Faculty Bibliography

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

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

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

Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients

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

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

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