Roberta M. Goldring, M.D.

Lung pathologic findings in a local residential and working community exposed to world trade center dust, gas, and fumes
Caplan-Shaw, Caralee E; Yee, Herman; Rogers, Linda; Abraham, Jerrold L; Parsia, Sam S; Naidich, David P; Borczuk, Alain; Moreira, Andre; Shiau, Maria C; Ko, Jane P; Brusca-Augello, Geraldine; Berger, Kenneth I; Goldring, Roberta M; Reibman, Joan
2011 Sep;53(9):981-991, Journal of occupational & environmental medicine
OBJECTIVE: : To describe pathologic findings in symptomatic World Trade Center-exposed local workers, residents, and cleanup workers enrolled in a treatment program. METHODS: : Twelve patients underwent surgical lung biopsy for suspected interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests (group 2, n = 6). High-resolution computed axial tomography and pathologic findings were coded. Scanning electron microscopy with energy-dispersive x-ray spectroscopy was performed. RESULTS: : High-resolution computed axial tomography showed reticular findings (group 1) or normal or airway-related findings (group 2). Pulmonary function tests were predominantly restrictive. Interstitial fibrosis, emphysematous change, and small airway abnormalities were seen. All cases had opaque and birefringent particles within macrophages, and examined particles contained silica, aluminum silicates, titanium dioxide, talc, and metals. CONCLUSIONS: : In symptomatic World Trade Center-exposed individuals, pathologic findings suggest a common exposure resulting in alveolar loss and a diverse response to injury
— id: 137445, year: 2011, vol: 53, page: 981, stat: Journal Article,

Case-Control Study of Lung Function in World Trade Center Health Registry Area Residents and Workers
Friedman SM; Maslow CB; Reibman J; Pillai PS; Goldring RM; Farfel MR; Stellman SD; Berger KI
2011 Sep 1;184(5):582-589, American journal of respiratory & critical care medicine
RATIONALE: Residents and area workers who inhaled dust and fumes from the World Trade Center disaster reported lower respiratory symptoms in two World Trade Center Health Registry surveys (2003-2004 and 2006-2007), but lung function data were lacking. OBJECTIVES: To examine the relationship between persistent respiratory symptoms and pulmonary function in a nested case-control study of exposed adult residents and area workers 7-8 years post-9/11/2001. METHODS: Registrants reporting post-9/11 onset of a lower respiratory symptom in the first survey and the same symptom in the second survey were solicited as potential cases. Registrants without lower respiratory symptoms in either Registry survey were solicited as potential controls. Final case-control status was determined by lower respiratory symptoms at a third interview (the study), when spirometry and impulse oscillometry were also performed. MAIN RESULTS: We identified 180 cases and 473 controls. Cases were more likely than controls to have abnormal spirometry (19% versus 11%, P<0.05), and impulse oscillometry measurements of elevated airway resistance, R5 (68% versus 27%, P<0.0001) and frequency dependence of resistance, R5-20 (36% versus 7%, P<0.0001). When spirometry was normal, cases were more likely than controls to have elevated R5 and R5-20 (62% versus 25% and 27% versus 6% respectively, both P<0.0001). Associations between symptoms and oscillometry held when factors significant in bivariate comparisons (BMI, spirometry, exposures) were analyzed using logistic regression. CONCLUSIONS: This study links persistent respiratory symptoms and oscillometric abnormalities in WTC-exposed residents and area workers. Elevated R5 and R5-20 in cases despite normal spirometry suggested distal airway dysfunction as a mechanism for symptoms
— id: 137969, year: 2011, vol: 184, page: 582, stat: Journal Article,

Disparity between proximal and distal airway reactivity during methacholine challenge
Segal, Leopoldo N; Goldring, Roberta M; Oppenheimer, Beno W; Stabile, Alexandra; Reibman, Joan; Rom, William N; Weiden, Michael D; Berger, Kenneth I
2011 Jun;8(3):145-152, COPD: Journal of Chronic Obstructive Pulmonary Disease
There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV(1) change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R(5,) R(20)) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5-20 Hz (R(5-20)) and reactance area (AX). R(5) varied widely during MCT (range -0.8 - 11.3 cmH(2)O/L/s) and correlated poorly with change in FEV(1) (r = 0.17). Changes in R(5) reflected changes in both R(20) and R(5-20) (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R(20) increased only 0.3 cmH(2)O/L/s, while R(5-20) increased 0.7 cmH(2)O/L/s for every 1cmH(2)O/L/s change in R(5,) indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV(1) change (<5%), while R(5) increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV(1) and R(20)) and distal airway heterogeneity (R(5-20) and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV(1). This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment
— id: 134171, year: 2011, vol: 8, page: 145, stat: Journal Article,

Emerging exposures and respiratory health: world trade center dust
Rom, William N; Reibman, Joan; Rogers, Linda; Weiden, Michael D; Oppenheimer, Beno; Berger, Kenneth; Goldring, Roberta; Harrison, Denise; Prezant, David
2010 May;7(2):142-145, Proceedings of the American Thoracic Society
The attack on the World Trade Center (WTC) on 9/11/2001 produced a massive dust cloud with acute exposure, and the rubble pile burning over 3 months exposed more than 300,000 residents, rescue workers, and clean-up workers. Firefighters in the New York City Fire Department had significant respiratory symptoms characterized by cough, dyspnea, gastroesophageal reflux, and nasal stuffiness with a significant 1-year decline in FVC and FEV(1). Bronchial hyperreactivity measured by methacholine challenge correlated with bronchial wall thickening on CT scans. Compared with the NHANES III data for FVC and FEV(1), 32% of 2,000 WTC dust-exposed residents and clean-up workers were below the lower 5th percentile. The most common abnormality was a low FVC pattern, a finding similar to that also described for individuals in rescue and recovery activities. Among those complaining of respiratory symptoms and normal spirometry, almost half had abnormalities detected with impedance oscillometry consistent with distal airways' disease. Follow-up with the WTC Health Registry and the WTC Environmental Health Center will help discern whether treatment with anti-inflammatory medications or bronchodilators in those with respiratory symptoms may prevent the development of chronic obstructive pulmonary disease
— id: 109531, year: 2010, vol: 7, page: 142, stat: Journal Article,

Evolution of pattern of breathing during a spontaneous breathing trial predicts successful extubation
Segal, Leopoldo N; Oei, Erwin; Oppenheimer, Beno W; Goldring, Roberta M; Bustami, Rami T; Ruggiero, Salvatore; Berger, Kenneth I; Fiel, Stanley B
2010 Mar;36(3):487-495, Intensive care medicine
PURPOSE: Rapid shallow breathing may occur at any time during spontaneous breathing trials (SBT), questioning the utility of a single determination of the rapid shallow breathing index (RSBI). We hypothesize that change in RSBI during SBT may more accurately predict successful extubation than a single determination. METHODS: Prospective observational study. Seventy-two subjects were extubated. At 24 h, 63/72 remained extubated (Extubation Success), and 9 were re-intubated (Extubation Failure). Respiratory rate (RR), tidal volume (VT) and RSBI were measured every 30 min during 2-h T-piece SBT. Change in respiratory parameters was assessed as percent change from baseline. RESULTS: Initial RSBI was similar in Extubation Success and Extubation Failure groups (77.0 +/- 4.8, 77.0 +/- 4.8, p = ns). Nevertheless, RSBI tended to remain unchanged or decreased in the Extubation Success group; in contrast RSBI tended to increase in the Extubation Failure group because of either increased RR and/or decreased VT (p < 0.001 for mean percent change RSBI over time), indicating worsening of the respiratory pattern. Quantitatively, only 7/63 subjects of the Extubation Success group demonstrated increased RSBI >/=20% at any time during the SBT. In contrast, in the Extubation Failure group, RSBI increased in all subjects during the SBT, and eight of nine subjects demonstrated an increase greater than 20%. Thus, with a 2-h SBT the optimal threshold was a 20% increase (sensitivity = 89%, specificity = 89%). Similar results were obtained at 30 min (threshold = 5% increase). Percent change of RSBI predicted successful extubation even when initial values were >/=105. CONCLUSION: Percent change of RSBI during an SBT is a better predictor of successful extubation than a single determination of RSBI
— id: 106592, year: 2010, vol: 36, page: 487, stat: Journal Article,

Obstructive airways disease with air trapping among firefighters exposed to World Trade Center dust
Weiden, Michael D; Ferrier, Natalia; Nolan, Anna; Rom, William N; Comfort, Ashley; Gustave, Jackson; Zeig-Owens, Rachel; Zheng, Shugi; Goldring, Roberta M; Berger, Kenneth I; Cosenza, Kaitlyn; Lee, Roy; Webber, Mayris P; Kelly, Kerry J; Aldrich, Thomas K; Prezant, David J
2010 Mar;137(3):566-574, Chest
BACKGROUND: The World Trade Center (WTC) collapse produced a massive exposure to respirable particulates in New York City Fire Department (FDNY) rescue workers. This group had spirometry examinations pre-September 11, 2001, and post-September 11, 2001, demonstrating declines in lung function with parallel declines in FEV(1) and FVC. To date, the underlying pathophysiologic cause for this has been open to question. METHODS: Of 13,234 participants in the FDNY-WTC Monitoring Program, 1,720 (13%) were referred for pulmonary subspecialty evaluation at a single institution. Evaluation included 919 full pulmonary function tests, 1,219 methacholine challenge tests, and 982 high-resolution chest CT scans. RESULTS: At pulmonary evaluation (median 34 months post-September 11, 2001), median values were FEV(1) 93% predicted (interquartile range [IQR], 83%-101%), FVC 98% predicted (IQR, 89%-106%), and FEV(1)/FVC 0.78 (IQR, 0.72-0.82). The residual volume (RV) was 123% predicted (IQR, 106%-147%) with nearly all participants having normal total lung capacity, functional residual capacity, and diffusing capacity of carbon monoxide. Also, 1,051/1,720 (59%) had obstructive airways disease based on at least one of the following: FEV(1)/FVC, bronchodilator responsiveness, hyperreactivity, or elevated RV. After adjusting for age, gender, race, height and weight, and tobacco use, the decline in FEV(1) post-September 11, 2001, was significantly correlated with increased RV percent predicted (P < .0001), increased bronchodilator responsiveness (P < .0001), and increased hyperreactivity (P = .0056). CT scans demonstrated bronchial wall thickening that was significantly associated with the decline in FEV(1) post-September 11, 2001 (P = .024), increases in hyperreactivity (P < .0001), and increases in RV (P < .0001). Few had evidence for interstitial disease. CONCLUSIONS: Airways obstruction was the predominant physiologic finding underlying the reduction in lung function post-September 11, 2001, in FDNY WTC rescue workers presenting for pulmonary evaluation
— id: 109029, year: 2010, vol: 137, page: 566, stat: Journal Article,

Obesity hypoventilation syndrome
Berger, Kenneth I; Goldring, Roberta M; Rapoport, David M
2009 Jun;30(3):253-261, Seminars in respiratory & critical care medicine
The term obesity hypoventilation syndrome (OHS) refers to the combination of obesity and chronic hypercapnia that cannot be directly attributed to underlying cardiorespiratory disease. Despite a plethora of potential pathophysiological mechanisms for gas exchange and respiratory control abnormalities that have been described in the obese, the etiology of hypercapnia in OHS has been only partially elucidated. Of particular note, obesity and coincident hypercapnia are often associated with some form of sleep disordered breathing (apnea/hypopnea or sustained periods of hypoventilation). From a conceptual point of view, even transient reductions of ventilation from individual sleep disordered breathing events must produce acute hypercapnia during the period of low ventilation. What is less clear, however, is the link between these transient episodes of acute hypercapnia and the development of chronic sustained hypercapnia persisting into wakefulness. A unifying view of how this comes about is presented in the following review. In brief, our concept is that chronic sustained hypercapnia (as in obesity hypoventilation) occurs when the disorder of ventilation that produces acute hypercapnia interacts with inadequate compensation (both during sleep and during the periods of wakefulness); neither alone is sufficient to fully explain the final result. The following discussion will amplify on both the potential reasons for acute hypercapnia in the obese and on what is known about the failure of compensation that must occur in these subjects
— id: 99025, year: 2009, vol: 30, page: 253, stat: Journal Article,

Distal airway function assessed by oscillometry at varying respiratory rate: comparison with dynamic compliance
Oppenheimer, Beno W; Goldring, Roberta M; Berger, Kenneth I
2009 Jun;6(3):162-170, COPD: Journal of Chronic Obstructive Pulmonary Disease
Distal airways disease causes significant morbidity yet remains insufficiently identified. We hypothesize that: ( [1] ) when spirometry is normal impulse oscillometry may provide information about mechanical properties of the distal airways in a manner comparable to dynamic compliance and ( [2] ) variation of breathing frequency will influence oscillometric measurements similar to effects of breathing frequency on dynamic compliance. Fifty-three symptomatic subjects with normal large airway function (spirometry) were studied; distal airway dysfunction was identified by presence of frequency dependence of compliance (FDC). Oscillometric parameters evaluated were resistance at 20 Hz (R20) and 5-20 Hz (R(5-20)), reactance at 5 Hz (X5), and reactance area (AX). R20 correlated with airway resistance by esophageal manometry (r = 0.74, p < 0.001); X5 correlated with dynamic compliance at a respiratory rate of 60 bpm (r = 0.61, p < 0.001); R(5-20) and AX correlated with FDC (r = 0.48, p < 0.001; r = 0.53, p < 0.01). IOS indices were further evaluated at increased respiratory rate (RR40). Oscillometric parameters changed minimally at RR40 in normal subjects DeltaR20 = 0.20 +/- 0.08 cmH2O/L/s, DeltaR(5-20) = 0.10 +/- 0.03 cmH2O/L/s, DeltaAX = 0.33 +/- 0.19 cmH2O/L). However, in symptomatic subjects, while R20 increased minimally at RR40 (DeltaR20 = 0.37 +/- 0.10 cmH2O/L/s), R(5-20) and AX increased markedly (DeltaR(5-20) = 0.54 +/- 0.06 cmH2O/L/s, DeltaAX = 4.28 +/- 0.67 cmH2O/L) and reversed post bronchodilator. IOS evaluates physiology of the distal airways in a manner comparable to dynamic compliance. Elevated respiratory rate influences oscillometric parameters and must be considered when interpreting oscillometric data. IOS provides a non-invasive tool for assessment of distal airway function when spirometry is normal, which can be applied to various clinical settings including early diagnosis of COPD (GOLD stage 0), asthma in clinical remission and occupational/ environmental irritant exposure
— id: 103163, year: 2009, vol: 6, page: 162, stat: Journal Article,

Characteristics of a residential and working community with diverse exposure to World Trade Center dust, gas, and fumes
Reibman, Joan; Liu, Mengling; Cheng, Qinyi; Liautaud, Sybille; Rogers, Linda; Lau, Stephanie; Berger, Kenneth I; Goldring, Roberta M; Marmor, Michael; Fernandez-Beros, Maria Elena; Tonorezos, Emily S; Caplan-Shaw, Caralee E; Gonzalez, Jaime; Filner, Joshua; Walter, Dawn; Kyng, Kymara; Rom, William N
2009 May;51(5):534-541, Journal of occupational & environmental medicine
OBJECTIVE: To describe physical symptoms in those local residents, local workers, and cleanup workers who were enrolled in a treatment program and had reported symptoms and exposure to the dust, gas, and fumes released with the destruction of the World Trade Center (WTC) on September 11, 2001. METHODS: Symptomatic individuals underwent standardized evaluation and subsequent treatment. RESULTS: One thousand eight hundred ninety-eight individuals participated in the WTC Environmental Health Center between September 2005 and May 2008. Upper and lower respiratory symptoms that began after September 11, 2001 and persisted at the time of examination were common in each exposure population. Many (31%) had spirometry measurements below the lower limit of normal. CONCLUSIONS: Residents and local workers as well as those with work-associated exposure to WTC dust have new and persistent respiratory symptoms with lung function abnormalities 5 or more years after the WTC destruction
— id: 98897, year: 2009, vol: 51, page: 534, stat: Journal Article,

World Trade Center collapse produced airway injury and air trapping
Weiden MD; Ferrier N; Nolan A; Rom WN; Comfort A; Gustave J; Zheng S; Goldring R; Berger K; Cosenz K; Beringer A; Glass L; Lee R; Zeig-Owens R; Webber M; Prezant DJ
2009 ;179:A5852-A5852, American journal of respiratory & critical care medicine
— id: 101391, year: 2009, vol: 179, page: A5852, stat: Journal Article,

Potential mechanism for transition between acute hypercapnia during sleep to chronic hypercapnia during wakefulness in obstructive sleep apnea
Berger, Kenneth I; Norman, Robert G; Ayappa, Indu; Oppenheimer, Beno W; Rapoport, David M; Goldring, Roberta M
2008 ;605:431-436, Advances in experimental medicine & biology
This paper presents a series of experiments, both in patients and computer models, investigating the transition from acute to chronic hypercapnia in OSA. The data demonstrate that acute hypercapnia during periodic breathing occurs due to either reduction in magnitude of inter-event ventilation and/or reduction in inter-event ventilatory duration relative to duration of the preceding event. The transition between acute hypercapnia during sleep and chronic sustained hypercapnia during wakefulness may be determined by an interaction between respiratory control and renal handling of HCO3-
— id: 75678, year: 2008, vol: 605, page: 431, stat: Journal Article,

Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure
Oppenheimer, Beno W; Goldring, Roberta M; Herberg, Matthew E; Hofer, Ira S; Reyfman, Paul A; Liautaud, Sybille; Rom, William N; Reibman, Joan; Berger, Kenneth I
2007 Oct;132(4):1275-1282, Chest
RATIONALE: Following collapse of the World Trade Center (WTC), individuals reported new-onset respiratory symptoms. Despite symptoms, spirometry often revealed normal airway function. However, bronchial wall thickening and air trapping were seen radiographically in some subjects. We hypothesized that symptomatic individuals following exposure to WTC dust may have functional abnormalities in distal airways not detectable with routine spirometry. METHODS: One hundred seventy-four subjects with respiratory symptoms and normal spirometry results were evaluated. Impedance oscillometry (IOS) was performed to determine resistance at 5 Hz, 5 to 20 Hz, and reactance area. Forty-three subjects were also tested for frequency dependence of compliance (FDC). Testing was repeated after bronchodilation. RESULTS: Predominant symptoms included cough (67%) and dyspnea (65%). Despite normal spirometry results, mean resistance at 5 Hz, 5 to 20 Hz, and reactance area were elevated (4.36 +/- 0.12 cm H(2)O/L/s, 0.86 +/- 0.05 cm H(2)O/L/s, and 6.12 +/- 0.50 cm H(2)O/L, respectively) [mean +/- SE]. Resistance and reactance normalized after bronchodilation. FDC was present in 37 of 43 individuals with improvement after bronchodilation. CONCLUSIONS: Symptomatic individuals with presumed WTC dust/fume exposure and normal spirometry results displayed airway dysfunction based on the following: (1) elevated airway resistance and frequency dependence of resistance determined by IOS; (2) heterogeneity of distal airway function demonstrated by elevated reactance area on oscillometry and FDC; and (3) reversibility of these functional abnormalities to or toward normal following administration of a bronchodilator. Since spirometry results were normal in all subjects, these abnormalities likely reflect dysfunction in airways more distal to those evaluated by spirometry. Examination of distal airway function when spirometry results are normal may be important in the evaluation of subjects exposed to occupational and environmental hazards
— id: 75380, year: 2007, vol: 132, page: 1275, stat: Journal Article,

Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model
Norman, Robert G; Goldring, Roberta M; Clain, Jeremy M; Oppenheimer, Beno W; Charney, Alan N; Rapoport, David M; Berger, Kenneth I
2006 May;100(5):1733-1741, Journal of applied physiology (Bethesda)
Acute hypercapnia may develop during periodic breathing from an imbalance between abnormal ventilatory patterns during apnea and/or hypopnea and compensatory ventilatory response in the interevent periods. However, transition of this acute hypercapnia into chronic sustained hypercapnia during wakefulness remains unexplained. We hypothesized that respiratory-renal interactions would play a critical role in this transition. Because this transition cannot be readily addressed clinically, we modified a previously published model of whole-body CO2 kinetics by adding respiratory control and renal bicarbonate kinetics. We enforced a pattern of 8 h of periodic breathing (sleep) and 16 h of regular ventilation (wakefulness) repeated for 20 days. Interventions included varying the initial awake respiratory CO2 response and varying the rate of renal bicarbonate excretion within the physiological range. The results showed that acute hypercapnia during periodic breathing could transition into chronic sustained hypercapnia during wakefulness. Although acute hypercapnia could be attributed to periodic breathing alone, transition from acute to chronic hypercapnia required either slowing of renal bicarbonate kinetics, reduction of ventilatory CO2 responsiveness, or both. Thus the model showed that the interaction between the time constant for bicarbonate excretion and respiratory control results in both failure of bicarbonate concentration to fully normalize before the next period of sleep and persistence of hypercapnia through blunting of ventilatory drive. These respiratory-renal interactions create a cumulative effect over subsequent periods of sleep that eventually results in a self-perpetuating state of chronic hypercapnia
— id: 66996, year: 2006, vol: 100, page: 1733, stat: Journal Article,

Membrane diffusion in diseases of the pulmonary vasculature
Oppenheimer, Beno W; Berger, Kenneth I; Hadjiangelis, Nicos P; Norman, Robert G; Rapoport, David M; Goldring, Roberta M
2006 Jul;100(7):1247-1253, Respiratory medicine
INTRODUCTION: We examined pulmonary diffusing capacity (D(LCO)) and its partition in pulmonary vascular diseases without evident parenchymal disease to assess the pattern and proportionality of change in membrane diffusion (D(m)) and capillary blood volume (V(c)). Disproportionate reduction in D(m) relative to V(c) (low D(m)/V(c)) in these diseases has been attributed to associated alveolar membrane/parenchymal disease, thus providing a potentially important diagnostic tool. METHODS: Diseases included: idiopathic pulmonary arterial hypertension (n=6), chronic thromboembolic disease (n=5), and intravenous drug use (n=14), providing a spectrum of pulmonary vascular diseases. V(c) and D(m) were determined as described by Roughton and Forster. RESULTS: All diseases showed a reduced V(c) (59+/-10, 69+/-14, 71+/-21 % predicted, respectively) and D(m) (76+/-22, 53+/-19, 63+/-16 % predicted, respectively) with no differences between groups (p>0.05). Disproportionate reduction of D(m) (D(m)/V(c) % predicted <1) was seen in all diseases (range 0.36-1.89). A mathematical analysis is presented to illustrate that changes in vascular geometry may additionally influence the proportionality of changes in D(m) and V(c). The mathematical analysis suggests that when reduction in patency of some vessels co-exits with compensatory dilatation of the remaining vasculature, a disproportionate reduction in D(m) relative to V(c) may result. CONCLUSIONS: The balance between vascular curtailment and compensatory dilatation may contribute to the variability of the D(m)/V(c) relationship seen in pulmonary vascular disease. Disproportionate reduction in D(m) relative to V(c) may result from this imbalance and need not imply subclinical alveolar membrane and/or parenchymal disease
— id: 80838, year: 2006, vol: 100, page: 1247, stat: Journal Article,

Effect of circulatory congestion on the components of pulmonary diffusing capacity in morbid obesity
Oppenheimer, Beno W; Berger, Kenneth I; Rennert, Douglas A; Pierson, Richard N; Norman, Robert G; Rapoport, David M; Kral, John G; Goldring, Roberta M
2006 Jul;14(7):1172-1180, Obesity (Silver Spring)
OBJECTIVE: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (DLCO) and capillary blood volume (Vc) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (Dm) is uncertain. We examined DLCO and its partition into Vc and Dm in 13 severely obese subjects (BMI = 51 +/- 14 kg/m2) without manifest cardiopulmonary disease before and after surgically induced weight loss. RESEARCH METHODS AND PROCEDURES: DLCO and its partition into Vc and Dm [referenced to alveolar volume (VA)] as described by Roughton and Forster, total body water by tritiated water, and fat distribution by waist-to-hip ratio were performed. RESULTS: Despite normal DLCO (mean 98 +/- 16% predicted), Vc/VA was increased (mean 118 +/- 30% predicted), and Dm/VA was reduced (mean 77 +/- 34% predicted). Nine of 13 subjects were restudied after weight loss (mean 52 +/- 43 kg); Vc/VA decreased to 89 +/- 18% predicted (p = 0.01), and Dm/VA increased to 139 +/- 30% predicted (p < 0.01). Increasing total body water was associated with both increasing Vc (r = 0.74, p = 0.01) and increasing waist-to-hip ratio (r = 0.65, p = 0.02), indicating that circulatory congestion increases with increasing central obesity. DISCUSSION: Severely obese subjects without manifest cardiopulmonary disease may have increased Vc indicating central circulatory congestion and reduced Dm suggesting associated alveolar capillary leak, despite normal DLCO. Reversibility with weight loss is in accord with reversibility of the hemodynamic abnormalities of obesity
— id: 80841, year: 2006, vol: 14, page: 1172, stat: Journal Article,

Magnetic resonance imaging-based spirometry for regional assessment of pulmonary function
Voorhees, Abram; An, Jing; Berger, Kenneth I; Goldring, Roberta M; Chen, Qun
2005 Oct;54(5):1146-1154, Magnetic resonance in medicine
In this work MRI-based spirometry is presented as a method for noninvasively assessing pulmonary mechanical function on a regional basis. A SPAMM tagging sequence was modified to allow continuous dynamic imaging of the lungs during respiration. A motion-tracking algorithm was developed to track material regions from time-resolved grid-tagged images. Experiments were performed to image the lungs during quiet breathing and volumetric strain was calculated from the measured displacement maps. Regional volume calculations, derived from volumetric strain, were integrated over the entire lung and compared to segmented volume calculations with good agreement. Results from this work demonstrate that MRI spirometry has the potential to become a clinically useful tool for measuring regional ventilation and assessing pulmonary diseases that regionally affect the mechanical function of the lung. Magn Reson Med, 2005. (c) 2005 Wiley-Liss, Inc.
— id: 58187, year: 2005, vol: 54, page: 1146, stat: Journal Article,

Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis
Addrizzo-Harris, D J; Harkin, T J; Tchou-Wong, K M; McGuinness, G; Goldring, R; Cheng, D; Rom, D W N
2002 ;180(2):61-72, Lung
The objective of this study was to evaluate the mechanisms of colchicine action in pulmonary fibrosis. The study included 10 patients with pulmonary fibrosis (idiopathic pulmonary fibrosis 5, asbestosis 4, and scleroderma 1) who had been admitted to Bellevue Hospital Center, a tertiary care public hospital in New York City. We administered colchicine 0.6 mg orally for 12 weeks to patients with pulmonary fibrosis. Symptoms, high resolution CT scans, pulmonary function tests, and bronchoalveolar lavage parameters were compared prior to and after treatment. Results showed declines in dyspnea index, selective improvement in several CT scans, but no statistically significant change in BAL cells, cytokines, fibronectin, or hydroxyproline. However, there was a decline in hydroxyproline in the BAL fluid in 8/10 patients. We concluded that colchicine has a mild antifibrotic effect which may be in inhibiting collagen formation since there was no effect on the inflammation that accompanies fibrosis
— id: 34535, year: 2002, vol: 180, page: 61, stat: Journal Article,

Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome
Ayappa, Indu; Berger, Kenneth I; Norman, Robert G; Oppenheimer, Beno W; Rapoport, David M; Goldring, Roberta M
2002 Oct 15;166(8):1112-1115, American journal of respiratory & critical care medicine
Prevention of acute hypercapnia during obstructive events in obstructive sleep apnea requires a balance between carbon dioxide (CO(2)) loading during the event and CO(2) unloading in the interevent period. Earlier studies have demonstrated that acute CO(2) retention may occur despite high interevent ventilation when the interevent duration is short relative to the duration of the preceding event. The present study examines the relationship between apnea and interapnea durations and relates this assessment of ventilatory periodicity to the degree of chronic hypercapnia in subjects with severe sleep apnea. A total of 18 subjects with sleep apnea (> 40 apnea/hour; chronic awake Pa(CO2) 36-62 mm Hg) and without underlying lung disease underwent polysomnography. For each event, apnea duration, interapnea duration, and apnea/interapnea duration ratio were determined. No relationship was observed between chronic Pa(CO2) and mean apnea or interapnea duration (p > 0.1). However, Pa(CO2) was directly related to apnea/interapnea duration ratio (r = 0.48; p < 0.05) such that with increasing chronic hypercapnia the interapnea duration shortens relative to the apnea duration. The present study suggests that control of the interapnea ventilatory duration relative to the duration of the preceding apnea, is an important component of the integrated ventilatory response to CO(2) loading during apnea and may contribute toward the development and/or maintenance of chronic hypercapnia in obstructive sleep apnea/hypopnea syndrome
— id: 39396, year: 2002, vol: 166, page: 1112, stat: Journal Article,

Postevent ventilation as a function of CO(2) load during respiratory events in obstructive sleep apnea
Berger, Kenneth I; Ayappa, Indu; Sorkin, I Barry; Norman, Robert G; Rapoport, David M; Goldring, Roberta M
2002 Sep;93(3):917-924, Journal of applied physiology (Bethesda)
Maintenance of eucapnia during sleep in obstructive sleep apnea (OSA) requires a balance between CO(2) loading during apnea and CO(2) elimination. This study examines individual respiratory events and relates magnitude of postevent ventilation to CO(2) load during the preceding respiratory event in 14 patients with OSA (arterial PCO(2) 42-56 Torr). Ventilation and expiratory CO(2) and O(2) fractions were measured on a breath-by-breath basis during daytime sleep. Calculations included CO(2) load during each event (metabolic CO(2) production - exhaled CO(2)) and postevent ventilation in the 10 s after an event. In 12 of 14 patients, a direct relationship existed between postevent ventilation and CO(2) load during the preceding event (P < 0.05); the slope of this relationship varied across subjects. Thus the postevent ventilation is tightly linked to CO(2) loading during each respiratory event and may be an important mechanism that defends against development of acute hypercapnia in OSA. An inverse relationship was noted between this postevent ventilatory response slope and the chronic awake arterial PCO(2) (r = 0.90, P < 0.001), suggesting that this mechanism is impaired in patients with chronic hypercapnia. The link between development of acute hypercapnia during respiratory events asleep and maintenance of chronic awake hypercapnia in OSA remains to be further investigated
— id: 39413, year: 2002, vol: 93, page: 917, stat: Journal Article,

Asthma in the elderly: cockroach sensitization and severity of airway obstruction in elderly nonsmokers
Rogers, Linda; Cassino, Cara; Berger, Kenneth I; Goldring, Roberta M; Norman, Robert G; Klugh, Thomas; Reibman, Joan
2002 Nov;122(5):1580-1586, Chest
STUDY OBJECTIVES: To test the hypothesis that the presence of sensitization to indoor allergens is associated with increased severity of airway obstruction in elderly subjects with asthma. DESIGN: Cohort study of subjects enrolled in a public hospital asthma clinic. SETTING: Asthma clinic in a municipal public hospital serving an indigent population in New York City. PATIENTS: Subjects aged > or = 60 years with asthma who were enrolled in the Bellevue Hospital Asthma Clinic. Total serum IgE and allergen-specific IgE measurements were performed in a cohort of elderly never-smokers who had asthma (45 patients) who had undergone spirometry before and after bronchodilator (BD) therapy. MEASUREMENTS AND RESULTS: The results of radioallergosorbent tests demonstrated that most subjects (ie, 60%) were sensitized to at least one allergen, with many sensitized to at least one indoor allergen. Cockroach (CR) was the most common allergen to which subjects were sensitized, with 47% displaying an elevated serum-specific IgE level. Fewer subjects were sensitized to dust mite, cat, dog, or ragweed. Subjects sensitized to CR (CR+) had greater reductions in airflow compared to subjects not sensitized to CR (CR-) [64 +/- 4.4% predicted vs 77.1 +/- 4.1% predicted FEV(1), respectively; p < 0.05]. Following BD administration, only 29% of CR+ subjects achieved a normal post-BD FEV(1) compared to 58% of CR- subjects. Lung volume measurements differed between CR+ and CR- subjects, with a greater elevation of functional residual capacity in CR+ subjects. CONCLUSION: In a population of elderly urban patients with asthma, the presence of CR-specific serum IgE is associated with more severe asthma, as reflected by an increase in airway obstruction and hyperinflation
— id: 39563, year: 2002, vol: 122, page: 1580, stat: Journal Article,

Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep
Berger KI; Ayappa I; Chatr-Amontri B; Marfatia A; Sorkin IB; Rapoport DM; Goldring RM
2001 Oct;120(4):1231-1238, Chest
OBJECTIVE: To identify the spectrum of respiratory disturbances during sleep in patients with obesity hypoventilation syndrome (OHS) and to examine the response of hypercapnia to treatment of the specific ventilatory sleep disturbances. DESIGNS AND METHODS: Twenty-three patients with chronic awake hypercapnia (mean [+/- SD] PaCO(2), 55 +/- 6 mm Hg) and a respiratory sleep disorder were retrospectively identified. Nocturnal polysomnography testing was performed, and flow limitation (FL) was identified from the inspiratory flow-time contour. Obstructive hypoventilation was inferred from sustained FL coupled with O(2) desaturation that was corrected with treatment of the upper airway obstruction. Central hypoventilation was inferred from sustained O(2) desaturation that persisted after the correction of the upper airway obstruction. Treatment was initiated, and follow-up awake PaCO(2) measurements were obtained (follow-up range, 4 days to 7 years). RESULTS: A variable number of obstructive sleep apneas/hypopneas (ie, obstructive sleep apnea-hypopnea syndrome [OSAHS]) were noted (range, 9 to 167 events per hour of sleep). Of 23 patients, 11 demonstrated upper airway obstruction alone (apnea-hypopnea/FL) and 12 demonstrated central sleep hypoventilation syndrome (SHVS) in addition to a variable number of OSAHS. Treatment aimed at correcting the specific ventilatory abnormalities resulted in correction of the chronic hypercapnia in all compliant patients (compliant patients: pretreatment, 57 +/- 6 mm Hg vs post-treatment, 41 +/- 4 mm Hg [p < 0.001]; noncompliant patients: pretreatment, 52 +/- 6 mm Hg vs post-treatment, 51 +/- 3 mm Hg; [difference not significant]). CONCLUSIONS: This study demonstrates that OHS encompasses a variety of distinct pathophysiologic disturbances that cannot be distinguished clinically at presentation. Sustained obstructive hypoventilation due to partial upper airway obstruction was demonstrated as an additional mechanism for OHS that is not easily classified as SHVS or OSAHS
— id: 26607, year: 2001, vol: 120, page: 1231, stat: Journal Article,

CO(2) homeostasis during periodic breathing in obstructive sleep apnea
Berger KI; Ayappa I; Sorkin IB; Norman RG; Rapoport DM; Goldring RM
2000 Jan;88(1):257-264, Journal of applied physiology (Bethesda)
The contribution of apnea to chronic hypercapnia in obstructive sleep apnea (OSA) has not been clarified. Using a model (D. M. Rapoport, R. G. Norman, and R. M. Goldring. J. Appl. Physiol. 75: 2302-2309, 1993), we previously illustrated failure of CO(2) homeostasis during periodic breathing resulting from temporal dissociation between ventilation and perfusion ('temporal V/Q mismatch'). This study measures acute kinetics of CO(2) during periodic breathing and addresses interapnea ventilatory compensation for maintenance of CO(2) homeostasis in 11 patients with OSA during daytime sleep (37-171 min). Ventilation and expiratory CO(2) and O(2) fractions were measured on a breath-by-breath basis by means of a tight-fitting full facemask. Calculations included CO(2) excretion, metabolic CO(2) production, and CO(2) balance (metabolic CO(2) production - exhaled CO(2)). CO(2) balance was tabulated for each apnea/hypopnea event-interevent cycle and as a cumulative value during sleep. Cumulative CO(2) balance varied (-3,570 to +1,388 ml). Positive cumulative CO(2) balance occurred in the absence of overall hypoventilation during sleep. For each cycle, positive CO(2) balance occurred despite increased interevent ventilation to rates as high as 45 l/min. This failure of CO(2) homeostasis was dependent on the event-to-interevent duration ratio. The results demonstrate that 1) periodic breathing provides a mechanism for acute hypercapnia in OSA, 2) acute hypercapnia during periodic breathing may occur without a decrease in average minute ventilation, supporting the presence of temporal V/Q mismatch, as predicted from our model, and 3) compensation for CO(2) accumulation during apnea/hypopnea may be limited by the duration of the interevent interval. The relationship of this acute hypercapnia to sustained chronic hypercapnia in OSA remains to be further explored
— id: 11860, year: 2000, vol: 88, page: 257, stat: Journal Article,

Duration of asthma and physiologic outcomes in elderly nonsmokers
Cassino C; Berger KI; Goldring RM; Norman RG; Kammerman S; Ciotoli C; Reibman J
2000 Oct;162(4 Pt 1):1423-1428, American journal of respiratory & critical care medicine
Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead to airway remodeling, which can result in physiologic abnormalities. Elderly lifetime nonsmokers are an ideal population in which to examine the consequences of longstanding asthma. To test the hypothesis that airflow limitation and hyperinflation are associated with the duration of asthma, we evaluated airflow and lung volumes in a cohort of elderly asthmatic individuals. All subjects were > 60 yr of age and were lifetime nonsmokers (n = 75). Patients with asthma of long duration (LDA; n = 38) had asthma for >/= 26 yr (median = 40.0 yr); patients with asthma of short duration (SDA; n = 37) had asthma for < 26 yr (median = 9 yr). Patients with LDA had a significantly lower FEV(1)% predicted than did those with SDA (59.5 +/- 2.6% versus 73.8 +/- 3.1% [mean +/- SEM], respectively; p < 0.007). Regression analysis demonstrated that duration of asthma was inversely associated with FEV(1)% predicted (r = 0.264, p < 0.03). After bronchodilator administration, the patients with LDA continued to show airflow obstruction (FEV(1)% predicted = 65.4 +/- 2.9). Only 18% of patients with LDA attained a normal postbronchodilator FEV(1), whereas 50% of those with SDA were able to do so (p < 0.003). The FRC% predicted was significantly higher in subjects with LDA than in those with SDA (142.9 +/- 5.6 versus 124.1 +/- 4.4, respectively, p < 0.01). Multiple regression analysis revealed an association between FRC and duration of asthma that was independent of the degree of airflow limitation. These data suggest that the duration of asthma is associated with the degree of airflow limitation and hyperinflation. Moreover, these abnormalities can become irreversible over time, and may reflect distal airway and/or parenchymal changes as well as proximal airway remodeling
— id: 39539, year: 2000, vol: 162, page: 1423, stat: Journal Article,

Frequency dependence of compliance in the evaluation of patients with unexplained respiratory symptoms [In Process Citation]
de la Hoz RE; Berger KI; Klugh TT; Friedman-Jimenez G; Goldring RM
2000 Mar;94(3):221-227, Respiratory medicine
Frequency dependence of compliance (FDC) reflects non-homogeneous ventilatory distribution and, in the presence of a normal measured airway resistance, suggests peripheral airways dysfunction. This study evaluated peripheral airway function and bronchial reactivity in irritant exposed or non-exposed individuals with normal routine pulmonary function tests (PFTs) who had persistent unexplained lower respiratory symptoms. Twenty-two patients were identified with persistent respiratory symptoms and with normal chest X-ray and PFTs. Twenty were non-smokers; two had stopped smoking more than 10 years before evaluation. Twelve patients had been exposed to irritants in their workplaces or at home. Non-specific bronchial hyper-reactivity (nsBHR) and FDC, pre- and post-bronchodilator, were measured in all patients. Studies were repeated in 6/12 irritant-exposed subjects after exposure removal and inhaled corticosteroid treatment. Whereas 12/22 patients had nsBHR, all 22 subjects demonstrated FDC [dynamic lung compliance/static lung compliance Cdyn,l/Cst,l at respiratory frequency 60 min(-1) (f60), mean 46%, range 27-67%]. After bronchodilator administration, a 15% improvement Cdyn,l was observed most consistently at f60 (mean% improvement 26%, 95% CI 14-38%) and in subjects without nsBHR. However, Cdyn,l at f60 did not return to normal after inhaled bronchodilator. Irritant-exposed and unexposed individuals appeared similar in results of testing for FDC and nsBHR. FDC and its response to bronchodilators provide objective physiological measures of an airway abnormality which may provide a basis for clinical symptoms in patients with normal routine pulmonary function studies. The presence of persistently abnormal FDC after bronchodilator (BD) and on follow up studies may reflect chronic inflammatory and/or structural changes in the airways in addition to bronchoconstriction
— id: 11733, year: 2000, vol: 94, page: 221, stat: Journal Article,

Periodic breathing and temporal V/Q mismatch in the genesis of acute hypercapnia in OSA
Berger, KI; Ayappa, I; Sorkin, IB; Norman, RG; Rapoport, DM; Goldring, RM
1999 MAR ;159(3):A785-A785, American journal of respiratory & critical care medicine
— id: 53894, year: 1999, vol: 159, page: A785, stat: Journal Article,

Effect of treatment on chronic hypercapnia in OHS
Chatraryamontri, B; Berger, KI; Ayappa, I; Sorkin, IB; Rapoport, DM; Goldring, RM
1999 MAR ;159(3):A784-A784, American journal of respiratory & critical care medicine
— id: 53893, year: 1999, vol: 159, page: A784, stat: Journal Article,

Mechanism of relief of tachypnea during pressure support ventilation
Berger KI; Sorkin IB; Norman RG; Rapoport DM; Goldring RM
1996 May;109(5):1320-1327, Chest
Pressure support ventilation (PSV) provides a range of ventilatory support from partial respiratory muscle unloading, where inspiratory work is shared between the patient and the mechanical ventilator, to total respiratory muscle unloading, where inspiratory work is performed solely by the ventilator. This study is designed to determine if minimizing work fully accounts for relief of tachypnea during PSV. We examined respiratory parameters over a range of PSV that includes the crossover from partial to total respiratory muscle unloading. Eight studies were obtained on seven intubated patients in respiratory failure. Ventilation, occlusion pressure (P0.1), and patient inspiratory work (WOBinsp) were measured while PSV was varied. In all patients, WOBinsp decreased as PSV increased. The level of PSV where WOBinsp was minimized was identified; this marked the crossover from partial to total respiratory muscle unloading. Frequency decreased with increasing PSV but remained elevated (range, 22 to 38 breaths/min) at the crossover. Frequency was normalized only at PSV levels 131 to 193% of the levels of pressure at the crossover. Tidal volume (VT) changed little during partial support and averaged 5.9 mL/kg at the crossover. VT increased only on PSV providing total unloading. Six of seven patients exhibited increasing static compliance with increasing VT suggesting alveolar recruitment. P0.1 tracked WOBinsp over the entire range of PSV (r = 0.95, p < 0.001). The normalization of frequency observed above the crossover coincided with increasing VT rather than decreasing work. These observations suggest that reflexes resulting from increased VT and/or alveolar recruitment may have contributed to the normalization of frequency
— id: 6981, year: 1996, vol: 109, page: 1320, stat: Journal Article,

Differentiation of the ILO boundary chest roentgenograph (0/1 to 1/0) in asbestosis by high-resolution computed tomography scan, alveolitis, and respiratory impairment
Harkin TJ; McGuinness G; Goldring R; Cohen H; Parker JE; Crane M; Naidich DP; Rom WN
1996 Jan;38(1):46-52, Journal of occupational & environmental medicine
High-resolution computed tomography (HRCT) scans have been advocated as providing greater sensitivity in detecting parenchymal opacities in asbestos-exposed individuals, especially in the presence of pleural fibrosis, and having excellent inter- and intraobserver reader interpretation. We compared the 1980 International Labor Organization (ILO) International Classification of the Radiographs of the Pneumoconioses for asbestosis with the high-resolution CT scan using a grid scoring system to better differentiate normal versus abnormal in the ILO boundary 0/1 to 1/0 chest roentgenograph. We studied 37 asbestos-exposed individuals using the ILO classification, HRCT grid scores, respiratory symptom questionnaires, pulmonary function tests, and bronchoalveolar lavage. We used Pearson correlation coefficients to evaluate the linear relationship between outcome variables and each roentgenographic method. The normal HRCT scan proved to be an excellent predictor of 'normality,' with pulmonary function values close to 100% for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO) and no increase in BAL inflammatory cells. Concordant HRCT/ILO abnormalities were associated with reduced FEV1/FVC ratio, reduced diffusing capacity, and alveolitis consistent with a definition of asbestosis. In our study, the ILO classification and HRCT grid scores were both excellent modalities for the assessment of asbestosis and its association with impaired physiology and alveolitis, with their combined use providing statistical associations with alveolitis and reduced diffusing capacity
— id: 56819, year: 1996, vol: 38, page: 46, stat: Journal Article,

Flow limitation as a noninvasive assessment of residual upper-airway resistance during continuous positive airway pressure therapy of obstructive sleep apnea
Condos R; Norman RG; Krishnasamy I; Peduzzi N; Goldring RM; Rapoport DM
1994 Aug;150(2):475-480, American journal of respiratory & critical care medicine
Many patients with obstructive sleep apnea syndrome (OSAS), despite therapy with nasal continuous positive airway pressure (CPAP), have persisting daytime somnolence that may be due to a persistently elevated upper-airway resistance associated with electroencephalographic (EEG) arousals. We tested the hypothesis that elevated upper-airway resistance can be inferred from the contour of the inspiratory flow tracing obtained from a conventional CPAP circuit. This may provide a noninvasive method for determining optimal CPAP. Data were collected during a CPAP titration of an upper-airway model and in eight patients with OSAS. Estimated inspiratory resistance was calculated from esophageal pressure, CPAP mask pressure, and inspiratory flow. At high CPAP, resistance was low and inspiratory flow contour was found to be rounded. At low CPAP, resistance was high and flow contour developed a plateau suggesting flow limitation. We also noted that the CPAP pressure at which high resistance developed, and at which flow limitation appeared, showed hysteresis. We conclude that when respiration is stable, the contour of inspiratory flow tracing from a CPAP system can be used to infer the presence of elevated upper-airway resistance and flow limitation. Optimizing flow contour may be an alternative to eliminating apneas in evaluation of the optimal therapeutic level of CPAP in OSAS
— id: 6339, year: 1994, vol: 150, page: 475, stat: Journal Article,

CO2 homeostasis during periodic breathing: predictions from a computer model
Rapoport DM; Norman RG; Goldring RM
1993 Nov;75(5):2302-2309, Journal of applied physiology (Bethesda)
The Bohr/Riley model of CO2 homeostasis describes the relationship between CO2 production, ventilation, and arterial PCO2 and assumes that ventilation and CO2 delivery to the lung are both anatomically and temporally well matched. In contrast to normal breathing, periodic patterns of ventilation show temporal mismatch of ventilation to CO2 delivery. We developed a computer model of lung CO2 clearance that uses CO2 transfer equations to generate iterative solutions for PCO2 in multiple body compartments as a function of time. During continuous ventilatory patterns our model predicts steady-state arterial PCO2 identical to that of the Bohr model. During periodic ventilation, we predict mean PCO2 will be elevated unless mean ventilation is increased above that required by the Bohr model. Waxing and waning tidal volumes, low functional residual capacity, and low capillary blood volume potentiate the hypercapnia. However, if cardiac output oscillates in phase with breathing, hypercapnia is minimized. This analysis suggests a new mechanism for the development of sustained hypercapnia, separate from absolute hypoventilation or the presence of lung disease
— id: 6491, year: 1993, vol: 75, page: 2302, stat: Journal Article,

EFFECT ON FRC OF EXTRATHORACIC NEGATIVE-PRESSURE DELIVERED BY A HAYEK OSCILLATOR
RAPOPORT, DM; PEDUZZI, N; NORMAN, RG; GOLDRING, RM
1993 APR ;147(4):A965-A965, American review of respiratory disease
— id: 54172, year: 1993, vol: 147, page: A965, stat: Journal Article,

Acute reversible hypoxemia in systemic lupus erythematosus
Abramson SB; Dobro J; Eberle MA; Benton M; Reibman J; Epstein H; Rapoport DM; Belmont HM; Goldring RM
1991 Jun 1;114(11):941-947, Annals of internal medicine
OBJECTIVE: To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products. DESIGN: Cohort study. SETTING: Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases. PATIENTS: Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls. MEASUREMENTS: Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured. MAIN RESULTS: Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL. CONCLUSION: A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation
— id: 9755, year: 1991, vol: 114, page: 941, stat: Journal Article,

Survival in patients with primary pulmonary hypertension. Results from a national prospective registry
D'Alonzo, G E; Barst, R J; Ayres, S M; Bergofsky, E H; Brundage, B H; Detre, K M; Fishman, A P; Goldring, R M; Groves, B M; Kernis, J T
1991 Sep 1;115(5):343-349, Annals of internal medicine
OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources
— id: 130423, year: 1991, vol: 115, page: 343, stat: Journal Article,

Endogenous opiates modulate the postapnea ventilatory response in the obstructive sleep apnea syndrome
Greenberg HE; Rapoport DM; Rothenberg SA; Kanengiser LA; Norman RG; Goldring RM
1991 Jun;143(6):1282-1287, American review of respiratory disease
Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 13999, year: 1991, vol: 143, page: 1282, stat: Journal Article,

Differing effects of the anxiolytic agents buspirone and diazepam on control of breathing
Rapoport DM; Greenberg HE; Goldring RM
1991 Apr;49(4):394-401, Clinical pharmacology & therapeutics
We compared ventilatory effects of the nonsedating anxiolytic buspirone with those of the sedating anxiolytic diazepam in nine normal men. Resting ventilatory parameters and ventilatory responses to CO2 rebreathing and inspiratory threshold loading were measured before and after placebo, diazepam, and buspirone. Placebo had no ventilatory effects. Diazepam had no effect on resting ventilation but depressed response to CO2. Buspirone had no effect on resting ventilation or CO2 response. During loading, buspirone did not alter the augmentation of mouth pressure; diazepam produced a trend toward less augmentation. Both anxiolytics altered the load compensation response for the group; in particular, an increase in ventilation during loading (seen in three of nine subjects) was suppressed by drug administration. Diazepam also markedly depressed one subject's loaded ventilation below unloaded ventilation. In summary, buspirone did not cause the depression of respiratory center chemosensitivity that was seen with diazepam and produced less depression of load compensation in normal subjects. This suggests that it may be a safer anxiolytic in patients with lung disease
— id: 14083, year: 1991, vol: 49, page: 394, stat: Journal Article,

Background ventilatory stimulus as a determinant of load compensation
Greenberg HE; Rapoport DM; Gloeggler PJ; Goldring RM
1989 Mar;66(3):1352-1358, Journal of applied physiology (Bethesda)
Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment
— id: 10716, year: 1989, vol: 66, page: 1352, stat: Journal Article,

Volume adjustment of mechanics and diffusion in interstitial lung disease. Lack of clinical relevance
Kanengiser LC; Rapoport DM; Epstein H; Goldring RM
1989 Nov;96(5):1036-1042, Chest
Relationships of lung mechanics and diffusion to lung volume were examined in 38 patients with interstitial lung disease to determine whether patterns of reduction relate to severity of disease, distinguish histologic characteristics or predict prognosis for reversibility. Normal volume-related values for both mechanics and diffusion were seen throughout the range of severity of disease. The ratio of mechanics to lung volume did not correlate with the ratio of diffusion to lung volume in the same patient. Volume relationships of mechanics and diffusion failed to distinguish pathologic predominance of fibrosis or inflammation/granulomas. These ratios failed to predict reversibility in patients who had repeated tests. These results suggest that in patients with interstitial lung disease the significance of 'volume-adjustment' of mechanics and diffusion should be viewed with caution; these parameters do not appear to contribute to the assessment of pathophysiology or correlate with clinical spectrum of interstitial lung diseases
— id: 10434, year: 1989, vol: 96, page: 1036, stat: Journal Article,

The acute administration of vasodilators in primary pulmonary hypertension. Experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension
Weir, E K; Rubin, L J; Ayres, S M; Bergofsky, E H; Brundage, B H; Detre, K M; Elliott, C G; Fishman, A P; Goldring, R M; Groves, B M
1989 Dec;140(6):1623-1630, American review of respiratory disease
The hemodynamic responses to acute vasodilator administration were evaluated in 163 patients who were entered into the National Institutes of Health Registry on Primary Pulmonary Hypertension (PPH) between 1981 and 1985. Of a total of 491 drug administrations in these patients, 135 administrations in 104 patients were performed in a manner acceptable to the Registry. A single vasodilator was tried in 79 patients and more than one vasodilator in 25 patients. Two-thirds of the patients were in New York Heart Association Functional Classes III or IV. When the effects of all vasodilators were grouped together, there were significant decreases from baseline in mean pulmonary artery pressure (60 +/- 2 to 57 +/- 2 mm Hg, p less than 0.05) and total pulmonary resistance index (32.5 +/- 1.7 to 25.1 +/- 1.4 mm Hg/L/min/m2, p less than 0.0001), and increases in cardiac index (2.1 +/- 0.1 to 2.7 +/- 0.1 L/min/m2, p less than 0.0001). Mean systemic blood pressure fell (88 +/- 1 to 79 +/- 1 mm Hg, p less than 0.0001), whereas PaO2 was unchanged (70 +/- 3 to 71 +/- 3 mm Hg, p = NS). A fall in total pulmonary resistance greater than 20% was observed in 55% of the adequate drug trials. Adverse effects occurred in 32 of the total 491 patient-drug trials and were generally minor. Hypotension requiring treatment developed in six patients. There were two deaths attributable to vasodilator administration. Patients who died or had hypotension requiring treatment had higher right atrial pressures than did other treated patients (15 +/- 2 versus 9 +/- 1 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 130428, year: 1989, vol: 140, page: 1623, stat: Journal Article,

COMPARISON OF THE EFFECTS OF BUSPIRONE AND DIAZEPAM ON CONTROL OF BREATHING
RAPOPORT, DM; GREENBERG, HE; GOLDRING, RM
1988 MAR 20 ;2(5):A1507-A1507, FASEB journal
— id: 51373, year: 1988, vol: 2, page: A1507, stat: Journal Article,

Primary pulmonary hypertension. A national prospective study
Rich, S; Dantzker, D R; Ayres, S M; Bergofsky, E H; Brundage, B H; Detre, K M; Fishman, A P; Goldring, R M; Groves, B M; Koerner, S K
1987 Aug;107(2):216-223, Annals of internal medicine
A national registry was begun in 1981 to collect data from 32 centers on patients diagnosed by uniform criteria as having primary pulmonary hypertension. Entered into the registry were 187 patients with a mean age (+/- SD) of 36 +/- 15 years (range, 1 to 81), and a female-to-male ratio of 1.7:1 overall. The mean interval from onset of symptoms to diagnosis was 2 years. The most frequent presenting symptoms included dyspnea (60%), fatigue (19%), and syncope (or near syncope) (13%). Raynaud phenomenon was present in 10% (95% of whom were female) and a positive antinuclear antibody test, in 29% (69% female). Pulmonary function studies showed mild restriction (forced vital capacity [FVC], 82% of predicted) with a reduced diffusing capacity for carbon monoxide (DLCO), and hypoxemia with hypocapnia. The mean (+/- SD) right atrial pressure was 9.7 +/- 6 mm Hg; mean pulmonary artery pressure, 60 +/- 18 mm Hg; cardiac index, 2.3 +/- 0.9 L/min X m2; and pulmonary vascular resistance index, 26 +/- 14 mm Hg/L/min X m2 for the group. Although no deaths or sustained morbid events occurred during the diagnostic evaluation of the patients, the typically long interval from initial symptoms to diagnosis emphasizes the need to develop strategies to make the diagnosis earlier
— id: 130432, year: 1987, vol: 107, page: 216, stat: Journal Article,

Respiratory failure in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia
Maxfield RA; Sorkin IB; Fazzini EP; Rapoport DM; Stenson WM; Goldring RM
1986 May;14(5):443-449, Critical care medicine
Seven patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia were studied to define the pathophysiology of their respiratory failure. The patients had fever, cough, dyspnea, hypoxemia, and diffuse infiltrates on chest x-ray. Biopsies revealed a spectrum of alveolar filling, interstitial edema and infiltration, and fibrosis. The patients were studied on mechanical ventilation to assess the effect of positive end-expiratory pressure (PEEP) and supplemental oxygen on shunt fraction. Mean anatomic shunt (measured on 100% oxygen) was 34 +/- 8%, which increased significantly (p less than .001) to 43 +/- 9% when the FIO2 was decreased to 40% to 60% (physiologic shunt), indicating ventilation/perfusion (V/Q) imbalance or impaired diffusion. Increasing PEEP by 9 +/- 2 cm H2O reduced the anatomic shunt to 30 +/- 7% (p less than .01) and the physiologic shunt to 37 +/- 7% (p less than .02). There was a similar decrease in anatomic and physiologic shunts in five studies, a greater decrease in physiologic shunt in four, and a greater decrease in anatomic shunt in two. Evidence of alveolar recruitment with PEEP, measured by an increase in static thoracic compliance, was found in only one study. There was no correlation between the effect of PEEP on compliance and its effect on shunt. The data suggest that in patients with AIDS and P. carinii pneumonia, PEEP can decrease shunt by reducing the anatomic shunt, improving V/Q imbalance, and converting areas of anatomic shunt to areas of low V/Q. P. carinii pneumonia in patients with AIDS can produce a clinical and pathophysiologic pattern similar to that described in the adult respiratory distress syndrome
— id: 57910, year: 1986, vol: 14, page: 443, stat: Journal Article,

Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome"
Rapoport DM; Garay SM; Epstein H; Goldring RM
1986 May;89(5):627-635, Chest
The mechanisms of hypercapnia in eight patients with the 'Pickwickian' syndrome and obstructive sleep apnea (OSAS) were evaluated pretherapy and posttherapy (tracheostomy in seven patients and chronic nocturnal use of nasal CPAP in one). Four patients (correctors) became eucapnic within two weeks of therapy. Four others (noncorrectors) remained hypercapnic. Neither residual apneas, changes in pulmonary function, change in anatomic dead space, nor changes in ventilatory chemoresponsiveness differentiated the two groups, nor did the last three factors account for return to eucapnia in the correctors. The results indicated two separate mechanisms exist for chronic hypercapnia in OSAS: a critical balance between the ventilation during the time spent awake and hypoventilation due to apneas, a mechanism removed by treatment for obstructive apnea; and sustained hypoventilation independent of the apnea phenomenon and therefore not correctible. The subset of patients with the second mechanism appears to represent the true 'Pickwickian' syndrome and can be identified before therapy by measuring a low level of ventilation in the sustained awake state
— id: 18497, year: 1986, vol: 89, page: 627, stat: Journal Article,

NONCARDIAC NON-PULMONARY FACTORS APPEAR TO LIMIT MAXIMAL EXERCISE PERFORMANCE IN PATIENTS ON CHRONIC-HEMODIALYSIS
RAPOPORT, DM; ROBERTSON, HT; GOLDBERG, L; GOLDRING, RM; ELLIOT, DL; AHMAD, S; KURTIN, P
1986 APR ;133(4):A46-A46, American review of respiratory disease
— id: 41466, year: 1986, vol: 133, page: A46, stat: Journal Article,

A CONSISTENT PATTERN OF EXERCISE IMPAIRMENT CHARACTERISTIC OF CHRONIC-HEMODIALYSIS (HD) PATIENTS
ROBERTSON, HT; RAPOPORT, DM; GOLDBERG, L; GOLDRING, RM; ELLIOT, DL; AHMAD, S; KURTIN, P
1986 JAN ;29(1):223-223, Kidney international
— id: 41521, year: 1986, vol: 29, page: 223, stat: Journal Article,

SPECIFIC DEFECTS IN CARDIOPULMONARY GAS-TRANSPORT - SUMMARY
GOLDRING, RM
1984 JAN 20 ;129(2):S57-S59, American review of respiratory disease
— id: 98599, year: 1984, vol: 129, page: S57, stat: Journal Article,

COMBINED VENTILATOR AND BICARBONATE STRATEGY IN THE MANAGEMENT OF STATUS-ASTHMATICUS - REPLY
MENITOVE, S; GOLDRING, R
1984 ;76(1):A88-A88, American journal of medicine
— id: 51027, year: 1984, vol: 76, page: A88, stat: Journal Article,

CO2 REBREATHING AND EXERCISE VENTILATORY RESPONSES IN HUMANS
MENITOVE, SM; RAPOPORT, DM; EPSTEIN, H; SORKIN, B; GOLDRING, RM
1984 ;56(4):1039-1044, Journal of applied physiology (Bethesda)
— id: 50892, year: 1984, vol: 56, page: 1039, stat: Journal Article,

RELATIONSHIP OF FUNCTIONAL RESIDUAL CAPACITY TO STATIC PULMONARY MECHANICS IN CHRONIC OBSTRUCTIVE PULMONARY-DISEASE
YIP, CK; EPSTEIN, H; GOLDRING, RM
1984 ;287(3):3-6, American journal of the medical sciences
— id: 50870, year: 1984, vol: 287, page: 3, stat: Journal Article,

HYPERCAPNIA IN POST TRACHEOSTOMY OBSTRUCTIVE SLEEP-APNEA (OSA)
GARAY, SM; RAPOPORT, DM; EPSTEIN, H; SORKIN, B; GOLDRING, RM
1983 ;127(4):235-235, American review of respiratory disease
— id: 50972, year: 1983, vol: 127, page: 235, stat: Journal Article,

COMBINED VENTILATOR AND BICARBONATE STRATEGY IN THE MANAGEMENT OF STATUS-ASTHMATICUS
MENITOVE, SM; GOLDRING, RM
1983 ;74(5):898-901, American journal of medicine
— id: 50962, year: 1983, vol: 74, page: 898, stat: Journal Article,

Nasal CPAP in obstructive sleep apnea: mechanisms of action
Rapoport DM; Garay SM; Goldring RM
1983 Nov-Dec;19(6):616-620, Bulletin europeean de physiopathologie respiratoire
Sixteen patients with the obstructive sleep apnea syndrome (OSAS) were studied for 1-2 h while receiving continuous positive airway pressure (CPAP) delivered via a nasal mask. Obstructive apneas were obliterated in all. Eight patients had studies of genioglossal muscle activity (GG EMG) and one patient had computed tomograms (CT) of the upper airway while on nasal CPAP. The GG EMG studies showed two patterns: suppression and augmentation of GG EMG while on CPAP. The CT scan showed the airway to be narrowed while the patient was awake off CPAP. It returned to a normal caliber when CPAP was applied, despite sleep. These results are interpreted to suggest three potential mechanisms of action for nasal CPAP in OSAS: 1) reduced upper airway resistance due to prevention of sleep-induced collapse of the airway; 2) reduced upper airway resistance due to dilatation of the airway by nasal CPAP beyond its dimension in the awake state; and 3) possible stimulation of mechanoreceptors leading to an increase in airway tone while CPAP is applied
— id: 18498, year: 1983, vol: 19, page: 616, stat: Journal Article,

GENIOGLOSSAL EMG (GGEMG) IN OBSTRUCTIVE SLEEP-APNEA (OSAS) - CART OR HORSE
RAPOPORT, DM; GOLDRING, RM
1983 ;127(4):236-236, American review of respiratory disease
— id: 50973, year: 1983, vol: 127, page: 236, stat: Journal Article,

NOCTURNAL NASAL-AIRWAY PRESSURE FOR SLEEP-APNEA - REPLY
RAPOPORT, DM; SORKIN, B; GARAY, SM; GOLDRING, RM
1983 ;308(8):462-462, New England journal of medicine
— id: 40739, year: 1983, vol: 308, page: 462, stat: Journal Article,

PATTERN OF DECLINE OF PULMONARY-FUNCTION IN MIDDLE-AGED CIGARETTE SMOKERS
Magnusson, B; Galdston, M; Goldring, R
1982 ;125(4):113-113, American review of respiratory disease
— id: 30418, year: 1982, vol: 125, page: 113, stat: Journal Article,

THE DIVERGENCE OF EXERCISE VENTILATION AND CO2 RESPONSIVENESS
MENITOVE, SM; RAPOPORT, DM; EPSTEIN, H; SORKIN, B; GOLDRING, RM
1982 ;125(4):210-210, American review of respiratory disease
— id: 50589, year: 1982, vol: 125, page: 210, stat: Journal Article,

Reversal of the "Pickwickian syndrome" by long-term use of nocturnal nasal-airway pressure
Rapoport DM; Sorkin B; Garay SM; Goldring RM
1982 Oct 7;307(15):931-933, New England journal of medicine
— id: 18499, year: 1982, vol: 307, page: 931, stat: Journal Article,

MECHANISM OF CHRONIC HYPERCAPNIA IN OBSTRUCTIVE SLEEP-APNEA (OSAS)
RAPOPORT, DM; GARAY, SM; EPSTEIN, H; GOLDRING, RM
1982 ;125(4):252-252, American review of respiratory disease
— id: 50590, year: 1982, vol: 125, page: 252, stat: Journal Article,

Regulation of ventilation in the obstructive sleep apnea syndrome
Garay SM; Rapoport D; Sorkin B; Epstein H; Feinberg I; Goldring RM
1981 Oct;124(4):451-457, American review of respiratory disease
The recent recognition of the sleep apnea syndrome has forced a re-evaluation of the mechanism of hypercapnia and disordered respiratory control in obese patients. Thirteen obese patients with sleep apnea were studied in an attempt to relate the pattern of sleep abnormality and awake ventilatory control to the presence of chronic hypercapnia. Patients with hypercapnia and/or hypoxemia had reduced ventilatory responses to hypercapnic and hypoxic stimulation, respectively. The presence of hypercapnia, however, did not separate the patients with respect to type, duration, or frequency of apneas. The degree of awake chemical drives could not be related to the severity of the sleep apnea phenomenon. However, patients with intact ventilatory control demonstrated augmented ventilation after apneas, which may explain their eucapnic state
— id: 18500, year: 1981, vol: 124, page: 451, stat: Journal Article,

Sustained reversal of chronic hypercapnia in patients with alveolar hypoventilation syndromes. Long-term maintenance with noninvasive nocturnal mechanical ventilation
Garay SM; Turino GM; Goldring RM
1981 Feb;70(2):269-274, American journal of medicine
Described in this study are eight patients with alveolar hypoventilation syndromes who presented with carbon dioxide narcosis and coma. After reversal of severe hypercapnia, all patients were discharged and maintained at home for an average period of 10 years utilizing 'noninvasive' nocturnal mechanical ventilation. The use of 'noninvasive' mechanical ventilation at home attempted to void the hazards of tracheostomy and the difficulties inherent in continuous daytime use of oxygen. This form of treatment has allowed these patients to continue their previously productive lives. This study represents the first published long-term follow-up regarding this mode of treatment in patients with alveolar hypoventilation
— id: 34081, year: 1981, vol: 70, page: 269, stat: Journal Article,

MECHANISMS OF HYPERCAPNIA IN OBESITY HYPOVENTILATION SYNDROME (OHS)
RAPOPORT, D; GARAY, S; EPSTEIN, H; SORKIN, B; SCHNEIDER, K; PERSKY, M; FEINBERG, I; GOLDRING, R
1981 ;29(2):A451-A451, Clinical research
— id: 40223, year: 1981, vol: 29, page: A451, stat: Journal Article,

FLOW-VOLUME CURVE CONTOUR IN COPD - CORRELATION WITH PULMONARY MECHANICS
JAYAMANNE, DS; EPSTEIN, H; GOLDRING, RM
1980 ;77(6):749-757, Chest
— id: 50069, year: 1980, vol: 77, page: 749, stat: Journal Article,

Canopy ventilation monitor for quantitative measurement of ventilation during sleep
Sorkin B; Rapoport DM; Falk DB; Goldring RM
1980 Apr;48(4):724-730, Journal of applied physiology. Respiratory, environmental & exercise physiology
A portable, easily assembled system that allows quantitative monitoring of ventilation in the sleeping human subject is described. It is a modification of the system used by Kinney et al. (Metab. Clin. Exp. 13: 205-211, 1964) and Spencer et al. (J. Appl. Physiol. 33: 523-528, 1972). The system directly measures gas flow without reliance on indirect CO2 or temperature sensors or on chest wall motion. It is comfortable and reflects the tidal volume with an accuracy of 92%. It also allows measurement of oxygen consumption and CO2 production. The gas breathed by the subject can be varied in composition. Two illustrative examples of the use of the system are given: 1) a case of obstructive apnea; and 2) a case in which a drop in arterial oxygen saturation is explained by quantified hypoventilation undetected by a nasal CO2 probe
— id: 57911, year: 1980, vol: 48, page: 724, stat: Journal Article,

Hermansky-Pudlak syndrome. Pulmonary manifestations of a ceroid storage disorder
Garay SM; Gardella JE; Fazzini EP; Goldring RM
1979 May;66(5):737-747, American journal of medicine
The Hermansky-Pudlak syndrome is a form of oculocutaneous albinism, characterized by a qualitative platelet defect and deposition of ceroid-like material throughout the reticuloendothelial system. During a 16 month period five patients with Hermansky-Pudlak syndrome presented with symptoms, chest films and pulmonary function studies consistent with restrictive pulmonary disease. In two patients, lung biopsies revealed diffuse interstitial fibrosis. However, light and electron microscopy demonstrated ceroid-like material within alveolar macrophages. In addition, two patients presented with inflammatory bowel disease with deposition of ceroid-like material in the colon. This disorder appears to be more common than is currently recognized and should be considered in the differential diagnosis of diffuse interstitial pulmonary disease and inflammatory bowel disease. A relationship between the deposition of ceroid-like material and pulmonary fibrosis is discussed in light of recent research concerning inflammatory processes. In view of the serious pulmonary, gastrointestinal and hematologic consequences of this syndrome, there is a need for genetic counseling of these patients
— id: 34082, year: 1979, vol: 66, page: 737, stat: Journal Article,

INFLUENCE OF LUNG-VOLUME ON EXPIRATORY FLOW-RATES IN DIFFUSE INTERSTITIAL LUNG-DISEASE
JAYAMANNE, DS; EPSTEIN, H; GOLDRING, RM
1978 ;275(3):329-336, American journal of the medical sciences
— id: 49947, year: 1978, vol: 275, page: 329, stat: Journal Article,

SLEEPING AND BREATHING
TURINO, GM; GOLDRING, RM
1978 ;299(18):1009-1010, New England journal of medicine
— id: 49928, year: 1978, vol: 299, page: 1009, stat: Journal Article,

EFFECT OF SERUM-CALCIUM ON INDUCED BICARBONATE EXCRETION
Feldman, G; Goldring, R; Kammerman, S
1977 ;25(3):A431-A431, Clinical research
— id: 29597, year: 1977, vol: 25, page: A431, stat: Journal Article,

Interactions of neutrophil elastase, serum trypsin inhibitory activity, and smoking history as risk factors for chronic obstructive pulmonary disease in patients with MM, MZ, and ZZ phenotypes for alpha-antitrypsin
Galdston, M; Melnick, E L; Goldring, R M; Levytska, V; Curasi, C A; Davis, A L
1977 Nov;116(5):837-846, American review of respiratory disease
— id: 76187, year: 1977, vol: 116, page: 837, stat: Journal Article,

Red cell 2,3-diphosphoglyceric acid and methemoglobin levels in workmen occupationally exposed to automobile exhaust
Goldstein, B D; Marks, C E Jr; Goldring, R M
1977 Feb 25;38(4):295-300, International archives of occupational & environmental health
— id: 108534, year: 1977, vol: 38, page: 295, stat: Journal Article,

INFLUENCE OF RECOIL PRESSURE ON MAXIMUM EXPIRATORY FLOW-VOLUME CURVE IN COPD
JAYAMANNE, DS; EPSTEIN, H; GOLDRING, RM
1977 ;36(3):493-493, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 40003, year: 1977, vol: 36, page: 493, stat: Journal Article,

PROTEASE-ANTIPROTEASE DETERMINANTS OF CHRONIC OBSTRUCTIVE PULMONARY-DISEASE (COPD)
Gladston, M; Goldring, R; Davis, AL
1976 ;35(3):631-631, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 28785, year: 1976, vol: 35, page: 631, stat: Journal Article,

ASSESSMENT OF RESPIRATORY REGULATION IN CHRONIC HYPERCAPNIA
GOLDRING, RM; TURINO, GM
1976 ;70(1):186-191, Chest
— id: 49720, year: 1976, vol: 70, page: 186, stat: Journal Article,

Role of circulatory congestion in the cardiorespiratory failure of obesity
Kaltman AJ; Goldring RM
1976 May 10;60(5):645-653, American journal of medicine
The role of circulatory congestion in the cardiorespiratory dysfunction of massive obesity was investigated in 18 patients. They were hypervolemic and had increased cardiac outputs proportionate to their weight. The average resting left ventricular filling pressure was within the upper limits of normal, but it increased to abnormally high levels with increased venous return of passive leg raising, and further during exercise. The elevations in pressure were associated with high resting central blood volumes which increased significantly with exertion. These findings are consistent with reduced distensibility of the central circulation in these congested patients. Weight reduction was accompanied by a decrease in central blood volumes and restoration of a normal left ventricular response in three of four patients and a return toward normal in one. The improvement in ventricular function with relief of edema and dyspnea. In 14 patients with normal or only minimal alveolar hypoventilation, there were no significant transpulmonary diastolic pressure gradients despite a marked increase in left ventricular end-diastolic pressures. One patient, after regaining weight, subsequently had an abnormal gas exchange and an increased pulmonary vascular resistance. He and two others with severe alveolar hypoventilation demonstrated cor pulmonale on a background of left ventricular dysfunction and congestion of the circulation. Two other patients, the least obese of the group, had hypoventilation and cor pulmonale with normal left ventricular pressures. Hypervolemia and a hyperdynamic state are common features of the obese patients. High cardiac output is maintained despite marked circulatory congestion which may result in generalized anasarca and increased ventricular filling pressures. This clinical syndrome may be present in obese patients without intrinsic heart disease and may be reversible with weight reduction. The central circulatory congestion may contribute to the development of the alveolar hypoventilation syndrome in certain obese patients
— id: 20306, year: 1976, vol: 60, page: 645, stat: Journal Article,

TECHNIQUES FOR MEASURING RESPONSIVENESS OF VENTILATORY APPARATUS IN MAN IN DISEASE
TURINO, GM; GOLDRING, RM
1976 ;70(1):180-185, Chest
— id: 49719, year: 1976, vol: 70, page: 180, stat: Journal Article,

Regulation of alveolar ventilation in respiratory failure
Goldring, R M; Heinemann, H O; Turino, G M
1975 Mar-Apr;269(2):160-170, American journal of the medical sciences
— id: 135834, year: 1975, vol: 269, page: 160, stat: Journal Article,

Bicarbonate and the regulation of ventilation
Heinemann, H O; Goldring, R M
1974 Sep;57(3):361-370, American journal of medicine
— id: 135835, year: 1974, vol: 57, page: 361, stat: Journal Article,

Correspondence: Chronic hypercapnia during methadone maintenance
Sapira, J D; Marks, C E Jr; Goldring, R M
1974 Apr;109(4):494-494, American review of respiratory disease
— id: 108533, year: 1974, vol: 109, page: 494, stat: Journal Article,

Renal response to mechanical ventilation in patients with chronic hypercapnia
Turino, G M; Goldring, R M; Heinemann, H O
1974 Feb;56(2):151-161, American journal of medicine
— id: 135836, year: 1974, vol: 56, page: 151, stat: Journal Article,

AVERAGE PULMONARY AIRWAY DIAMETERS FROM AEROSOL MEASUREMENTS WITH BREATH HOLDING
ALTSHULE.B; WANG, C; GOLDRING, RM; PALMES, ED
1973 ;32(3):415-&, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 39877, year: 1973, vol: 32, page: 415, stat: Journal Article,

ROLE OF CIRCULATORY CONGESTION IN CARDIORESPIRATORY FAILURE OF OBESITY
KALTMAN, AJ; GOLDRING, RM
1973 ;48(4):135-135, Circulation
— id: 39770, year: 1973, vol: 48, page: 135, stat: Journal Article,

Chronic hypercapnia during methadone maintenance
Marks, C E Jr; Goldring, R M
1973 Nov;108(5):1088-1093, American review of respiratory disease
— id: 108531, year: 1973, vol: 108, page: 1088, stat: Journal Article,

Cerebrospinal fluid acid-base relationships in ketoacidosis and lactic acidosis
Marks, C E Jr; Goldring, R M; Vecchione, J J; Gordon, E E
1973 Dec;35(6):813-819, Journal of applied physiology
— id: 108532, year: 1973, vol: 35, page: 813, stat: Journal Article,

Effect of depth of inhalation on aerosol persistence during breath holding
Palmes, E D; Wang, C S; Goldring, R M; Altshuler, B
1973 Mar;34(3):356-360, Journal of applied physiology
— id: 106664, year: 1973, vol: 34, page: 356, stat: Journal Article,

Respiratory-renal adjustments in chronic hypercapnia in man. Extracellular bicarbonate concentration and the regulation of ventilation
Goldring, R M; Turino, G M; Heinemann, H O
1971 Dec;51(6):772-784, American journal of medicine
— id: 135839, year: 1971, vol: 51, page: 772, stat: Journal Article,

Effect of chronic obstructive pulmonary disease on rate of deposition of aerosols in the lung during breath holding
Palmes, E D; Goldring, R M; Wang, C; Altshuler, B
1970 ;1:123-130, Inhaled particles
— id: 106669, year: 1970, vol: 1, page: 123, stat: Journal Article,

Respiratory adjustment to chronic metabolic alkalosis in man
Goldring RM; Cannon PJ; Heinemann HO; Fishman AP
1968 Jan;47(1):188-202, Journal of clinical investigation
This study examined the ventilatory adjustment to chronic metabolic alkalosis induced under controlled conditions in normal human volunteers. Metabolic alkalosis induced by buffers (sodium bicarbonate, trishydroxymethylamine methane) or ethacrynic acid was associated with alveolar hypoventilation, as evidenced by a rise in arterial Pco(2), a fall in arterial Po(2), a reduced resting tidal volume, and a diminished ventilatory response to CO(2) inhalation. Alveolar hypoventilation did not occur when metabolic alkalosis was induced in the same subjects by thiazide diuretics or aldosterone despite comparable elevations of the arterial blood pH and bicarbonate concentration.The different ventilatory responses of the two groups could not be ascribed to differences among individuals comprising each group, pharmacological effects of the alkalinizing agents, differences in the composition of the lumber spinal fluid, changes in extracellular fluid volume, or sodium and chloride balance.The differences in ventilatory adjustments were associated with differences in the patterns of hydrogen and potassium ion balance during the induction of alkalosis. Alveolar hypoventilation occurred when hydrogen ions were buffered (sodium bicarbonate, trishydroxymethylamine methane) or when renal hydrogen ion excretion was increased (ethacrynic acid). Alveolar hypoventilation did not occur when induction of similar degrees of extracellular alkalosis was accompanied by marked potassium loss and no demonstrable increase in external hydrogen loss (thiazides and aldosterone).These observations suggest that respiratory depression does not necessarily accompany extracellular alkalosis but depends on the effect of the mode of induction of the alkalosis on the tissues involved in the control of ventilation
— id: 96474, year: 1968, vol: 47, page: 188, stat: Journal Article,