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Isolated small airway reactivity during bronchoprovocation as a mechanism for respiratory symptoms in WTC dust-exposed community members

Berger, Kenneth I; Kalish, Samantha; Shao, Yongzhao; Marmor, Michael; Kazeros, Angeliki; Oppenheimer, Beno W; Chan, Yinny; Reibman, Joan; Goldring, Roberta M
INTRODUCTION: Small airway dysfunction occurs following WTC dust exposure, but its role in producing symptoms is unclear. METHODS: Methacholine challenge (MCT) was used to assess the relationship between onset of respiratory symptoms and small airway abnormalities in 166 symptomatic WTC dust-exposed patients. Forced oscillation testing (FOT) and respiratory symptoms were assessed during MCT. FOT parameters included resistance at 5 and 20 Hz (R5 and R20 ) and the R5 minus R20 (R5-20 ). RESULTS: Baseline spirometry was normal in all (mean FEV1 100 + 13% predicted, mean FEV1 /FVC 80 + 4%). MCT revealed bronchial hyperreactivity by spirometry in 67 patients. An additional 24 patients became symptomatic despite minimal FEV1 change (<5%); symptom onset coincided with increased R5 and R5-20 (P > 0.001 vs. baseline). The dose-response of FOT (reactivity) was greater compared with subjects that remained asymptomatic (P < 0.05). CONCLUSIONS: FOT during MCT uncovered reactivity in small airways as a mechanism for respiratory symptoms in subjects with inhalational lung injury. Am. J. Ind. Med. 59:767-776, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID: 27582479
ISSN: 1097-0274
CID: 2232062

Progression from respiratory dysfunction to failure in late-onset Pompe disease

Berger, Kenneth I; Chan, Yinny; Rom, William N; Oppenheimer, Beno W; Goldring, Roberta M
To identify determinants of respiratory disease progression in late-onset Pompe disease (LOPD), we studied relationships between pulmonary function, respiratory muscle strength, gas exchange, and respiratory control. Longitudinal evaluation of 22 LOPD patients (mean age 38 years) was performed at 6-month intervals for 6-24 months. Measurements included vital capacity (VC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), tidal volume (VT), dead space (VD), and ventilatory response to CO2. Although reduction in VC correlated with MIP and MEP (p < 0.0001), some patients had normal VC despite reduced MIP and MEP (5 [23%] and 9 [41%] patients, respectively). Daytime hypercapnia was associated with reduced VC (<60% predicted) and MIP (<40% predicted). Moreover, chronic hypercapnia was associated with elevated VD/VT (>/=0.44) due to falling VT ( approximately 300 ml), compatible with reduced efficiency of CO2 clearance. The presence of hypercapnia and/or ventilatory support was associated with reduced ventilatory responsiveness to CO2 (
PMID: 27297666
ISSN: 1873-2364
CID: 2145062

Non-Conventional Use Of Acetazolamide With Simultaneous Chloride Repletion In Severe Metabolic Alkalosis [Meeting Abstract]

Katzman, DP; Mirant-Borde, MC; Kline, M; Oppenheimer, BW
ISI:000390749601113
ISSN: 1535-4970
CID: 2414512

Dysfunction Of The Distal Airway And Alveolar Capillary Membrane (distal Lung Unit) During Steady State Exercise [Meeting Abstract]

Soghier, I; Smith, D; Berger, KI; Goldring, RM; Oppenheimer, BW
ISI:000390749604110
ISSN: 1535-4970
CID: 2414752

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity

Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M
RATIONALE: Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. OBJECTIVES: We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. METHODS: 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. MEASUREMENTS AND MAIN RESULTS: Mean age was 45+/-12 years; mean BMI was 44.8+/-7 kg/m2. Vital capacity was 88+/-13% predicted with reduction in functional residual capacity (58+/-12% predicted). Despite normal DLCO (98+/-18% predicted), VC was elevated (135+/-31% predicted) while DM averaged 94+/-22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. CONCLUSIONS: Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.
PMCID:4817979
PMID: 27035663
ISSN: 1932-6203
CID: 2059382

Rebuttal From Drs Berger, Goldring, and Oppenheimer

Berger, Kenneth I; Goldring, Roberta M; Oppenheimer, Beno W
We agree that the "holy grail" of pulmonary physiologists is a test that detects early chronic airway disease. While Dr. Enright remains "cautiously optimistic" that FOT can serve this purpose, there are sufficient data to mitigate his caution.
PMID: 26020419
ISSN: 1931-3543
CID: 1603702

Point: Should Oscillometry be used to Screen for Airway Disease: Yes

Berger, Kenneth I; Goldring, Roberta M; Oppenheimer, Beno W
Detection of airway disease by physiologic testing was initially described using spirometry to determine vital capacity and expiratory airflow under maximal effort to distinguish obstructive from restrictive disease processes. Subsequently, Dubois demonstrated direct assessment of airway resistance using plethysmography and in a separate publication described the precursor of the forced oscillation technique to measure respiratory system resistance. This review addresses the question of whether direct assessment of resistance by forced oscillation provides diagnostic information equivalent or superior to standard assessment of airflow rates by spirometry.
PMID: 26020800
ISSN: 1931-3543
CID: 1603722

Differing Mechanisms For Distal Lung Dysfunction In Obese Subjects With Nonallergic Asthma [Meeting Abstract]

Smith, D; Berger, KI; Goldring, RM; Soghier, I; Parikh, M; Oppenheimer, BW
ISI:000377582804169
ISSN: 1535-4970
CID: 2162072

Mind The Gap: Discrepancies Between Central And Mixed Venous Oxygen Saturations [Meeting Abstract]

Zakhary, B; Mukherjee, V; Kim, HM; Oppenheimer, B
ISI:000209838206014
ISSN: 1535-4970
CID: 2492902

Effect Of Weight Loss On Obesity Related Central Circulatory Congestion, Alveolar Membrane And Airway Function [Meeting Abstract]

Ali, S.; Soghier, I.; Goldring, R.; Berger, K. I.; Segal, L. N.; Ma, J.; Kalish, S.; Parikh, M.; Oppenheimer, B.
ISI:000209838202794
ISSN: 1073-449x
CID: 2960032