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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Current techniques for measuring absolute lung volumes rely on bulky and expensive equipment and are complicated to use for the operator and the patient. A novel method for measurement of absolute lung volumes, the MiniBox method, is presented., Research Question: Across a population of patients and healthy participants, do values for total lung capacity (TLC) determined by the novel compact device (MiniBox, PulmOne Advanced Medical Devices, Ltd.) compare favorably with measurements determined by traditional whole body plethysmography?, Study Design and Methods: A total of 266 participants (130 men) and respiratory patients were recruited from five global centers (three in Europe and two in the United States). The study population comprised individuals with obstructive (n = 197) and restrictive (n = 33) disorders as well as healthy participants (n = 36). TLC measured by conventional plethysmography (TLC Pleth ) was compared with TLC measured by the MiniBox (TLC MB )., Results: TLC values ranged between 2.7 and 10.9 L. The normalized root mean square difference (NSD) between TLC Pleth and TLC MB was 7.0% in healthy participants. In obstructed patients, the NSD was 7.9% in mild obstruction and 9.1% in severe obstruction. In restricted patients, the NSD was 7.8% in mild restriction and 13.9% in moderate and severe restriction. No significant differences were found between TLC values obtained by the two measurement techniques. Also no significant differences were found in results obtained among the five centers., Interpretation: TLC as measured by the novel MiniBox system is not significantly different from TLC measured by conventional whole body plethysmography, thus validating the MiniBox method as a reliable method to measure absolute lung volumes., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined., Methods: This study included 2,137 WTC-exposed firefighters who underwent a clinically indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001 and 9/10/2017. A post-BD FEV 1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV 1 /FVC ratio < 0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (n = 215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC exposure, first post-9/11 FEV 1 /FVC ratio, and BMI included as covariates., Results: BD-PFT diagnosed asthma/COPD overlap in 99 subjects (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration ≥ 300 cells/μL was associated with increased risk of asthma/COPD overlap (hazard ratio [HR], 1.85; 95% CI, 1.16-2.95) but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR, 1.51 per doubling of cytokine concentration; 95% CI, 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HRs of 1.73 [95% CI, 1.27-2.35] and 2.06 [95% CI, 1.31-3.23], respectively)., Conclusions: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The present study (1) characterizes a physiologic phenotype of restrictive dysfunction due to airway injury and (2) compares this phenotype to the phenotype of interstitial lung disease (ILD)., Methods: This is a retrospective study of 54 persistently symptomatic subjects following World Trade Center (WTC) dust exposure. Inclusion criteria were reduced vital capacity (VC), FEV1/VC>77%, and normal chest roentgenogram. Measurements included spirometry, plethysmography, diffusing capacity of lung for carbon monoxide (Dlco), impulse oscillometry (IOS), inspiratory/expiratory CT scan, and lung compliance (n=16)., Results: VC was reduced (46% to 83% predicted) because of the reduction of expiratory reserve volume (43%±26% predicted) with preservation of inspiratory capacity (IC) (85%±16% predicted). Total lung capacity (TLC) was reduced, confirming restriction (73%±8% predicted); however, elevated residual volume to TLC ratio (0.35±0.08) suggested air trapping (AT). Dlco was reduced (78%±15% predicted) with elevated Dlco/alveolar volume (5.3±0.8 [mL/mm Hg/min]/L). IOS demonstrated abnormalities in resistance and/or reactance in 50 of 54 subjects. CT scan demonstrated bronchial wall thickening and/or AT in 40 of 54 subjects; parenchymal disease was not evident in any subject. Specific compliance at functional residual capacity (FRC) (0.07±0.02 [L/cm H2O]/L) and recoil pressure (Pel) at TLC (27±7 cm H2O) were normal. In contrast to patients with ILD, lung expansion was not limited, since IC, Pel, and inspiratory muscle pressure were normal. Reduced TLC was attributable to reduced FRC, compatible with airway closure in the tidal range., Conclusions: This study describes a distinct physiologic phenotype of restriction due to airway dysfunction. This pattern was observed following WTC dust exposure, has been reported in other clinical settings (eg, asthma), and should be incorporated into the definition of restrictive dysfunction.

Background: This section of the guidelines is intended to provide an evidence-based approach to the preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer., Methods: The current guidelines and medical literature applicable to this issue were identified by computerized search and were evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee., Results: The preoperative physiologic assessment should begin with a cardiovascular evaluation and spirometry to measure the FEV1 and the diffusing capacity for carbon monoxide (Dlco). Predicted postoperative (PPO) lung functions should be calculated. If the % PPO FEV1 and % PPO Dlco values are both > 60%, the patient is considered at low risk of anatomic lung resection, and no further tests are indicated. If either the % PPO FEV1 or % PPO Dlco are within 60% and 30% predicted, a low technology exercise test should be performed as a screening test. If performance on the low technology exercise test is satisfactory (stair climbing altitude > 22 m or shuttle walk distance > 400 m), patients are regarded as at low risk of anatomic resection. A cardiopulmonary exercise test is indicated when the PPO FEV1 or PPO Dlco (or both) are < 30% or when the performance of the stair-climbing test or the shuttle walk test is not satisfactory. A peak oxygen consumption (V˙O2 peak) < 10 mL/kg/min or 35% predicted indicates a high risk of mortality and long-term disability for major anatomic resection. Conversely, a V˙O2 peak > 20 mL/kg/min or 75% predicted indicates a low risk., Conclusions: A careful preoperative physiologic assessment is useful for identifying those patients at increased risk with standard lung cancer resection and for enabling an informed decision by the patient about the appropriate therapeutic approach to treating his or her lung cancer. This preoperative risk assessment must be placed in the context that surgery for early-stage lung cancer is the most effective currently available treatment of this disease.

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.

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.

Background: Previous reports suggest that sarcoidosis occurs with abnormally high frequency in firefighters. We sought to determine whether exposure to World Trade Center (WTC) "dust" during the collapse and rescue/recovery effort increased the incidence of sarcoidosis or "sarcoid-like" granulomatous pulmonary disease (SLGPD)., Methods: During the 5 years after the WTC disaster, enrollees in the Fire Department of New York (FDNY) WTC monitoring and treatment programs who had chest radiograph findings suggestive of sarcoidosis underwent evaluation, including the following: chest CT imaging, pulmonary function, provocative challenge, and biopsy. Annual incidence rates were compared to the 15 years before the WTC disaster., Results: After WTC dust exposure, pathologic evidence consistent with new-onset sarcoidosis was found in 26 patients: all 26 patients had intrathoracic adenopathy, and 6 patients (23%) had extrathoracic disease. Thirteen patients were identified during the first year after WTC dust exposure (incidence rate, 86/100,000), and 13 patients were identified during the next 4 years (average annual incidence rate, 22/100,000; as compared to 15/100,000 during the 15 years before the WTC disaster). Eighteen of 26 patients (69%) had findings consistent with asthma. Eight of 21 patients (38%) agreeing to challenge testing had airway hyperreactivity (AHR), findings not seen in FDNY sarcoidosis patients before the WTC disaster., Conclusion: After the WTC disaster, the incidence of sarcoidosis or SLGPD was increased among FDNY rescue workers. This new information about the early onset of WTC-SLGPD and its association with asthma/AHR has important public health consequences for disease prevention, early detection, and treatment following environmental/occupational exposures.

Study Objective: To determine the benefits of daily use of high-frequency chest wall oscillation (HFCWO) in familial dysautonomia (FD) patients with lung disease., Design: Pulmonary function tests, chest radiographs, and blood tests were performed on entry to the study. A retrospective chart review of 12 months prior to entry provided baseline data regarding respiratory illnesses, medications, doctor visits, hospitalizations, and absenteeism. Daily logs provided prospective data on these parameters as well as HFCWO usage. Evaluations were performed at 1, 3, 6, 9, and 12 months for pulse oximetry, spirometry, and log review. At the exit evaluation, blood tests and chest radiographs were repeated., Patients: Fifteen FD patients with history of lung disease requiring daily inhalation therapy (7 female and 8 male; age range, 11 to 33 years) were enrolled in a 1-year clinical trial of HFCWO therapy. Two subjects withdrew after 3 months and 6 months, respectively. Each individual served as his/her own control., Results: Oxygen saturation improved by 1 month (median, 97.5%; interquartile range [IQR], 96 to 98%; vs median, 94%; IQR, 89 to 96%) and was sustained at exit evaluation (median, 98%; IQR, 98 to 98%) [p = 0.004]. Median FVC and peak expiratory flow rate (PEFR) were the pulmonary function measures with sustained improvement from baseline to exit (p = 0.02 and p = 0.03, respectively). When retrospective and prospective data were compared, all measured health outcomes improved significantly, including pneumonias (p = 0.0156), hospitalizations (p = 0.0161), antibiotic courses (p = 0.0005), antibiotic days (p = 0.0002), doctor visits (p = 0.0005), and absenteeism (p = 0.0002)., Conclusion: In this limited study of FD patients, HFCWO effected significant improvements in all measured health outcomes and oxygen saturation; FVC and PEFR were the pulmonary function measures demonstrating sustained improvement.

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.