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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 (TLCPleth) was compared with TLC measured by the MiniBox (TLCMB). Results TLC values ranged between 2.7 and 10.9 L. The normalized root mean square difference (NSD) between TLCPleth and TLCMB 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.

Objective To examine respiratory muscle function among late-onset Pompe disease (LOPD) patients in the Pompe Registry (NCT00231400/Sanofi Genzyme) during enzyme replacement therapy (ERT) with alglucosidase alfa by assessing the longitudinal course of forced vital capacity (FVC), prognostic factors for FVC, and impact of time from diagnosis to ERT initiation. Methods Longitudinal FVC data from LOPD (symptom onset > 12 months or ≤ 12 months without cardiomyopathy) patients were analyzed. Patients had to have baseline FVC (percent predicted upright) assessments at ERT start and ≥ 2 valid post-baseline assessments. Longitudinal analyses used linear mixed-regression models. Results Among 396 eligible patients, median baseline FVC was 66.9% (range 9.3–126.0). FVC remained stable during the 5-year follow-up (slope = − 0.17%, p = 0.21). Baseline FVC was lower among various subgroups, including patients who were male; older at ERT initiation; had a longer duration from symptom onset to ERT initiation; and had more advanced disease at baseline (based on respiratory support use, inability to ambulate, ambulation device use). Age at symptom onset was not associated with baseline degree of respiratory dysfunction. Differences between subgroups observed at baseline remained during follow-up. Shorter time from diagnosis to ERT initiation was associated with higher FVC after 5 years in all patients and the above subgroups using a cut-off of 1.7 years. Conclusion FVC stability over 5 years suggests that respiratory function is preserved during long-term ERT in real-world settings. Early initiation of alglucosidase alfa was associated with preservation of FVC in LOPD patients with better respiratory function at the time of treatment initiation.

Background Smoking cessation is the most effective means of slowing the decline of lung function associated with chronic obstructive pulmonary disease (COPD). While effective smoking cessation treatments are available, they are underutilized and nearly half of people with COPD continue to smoke. By addressing both nicotine and behavioral dependence, electronic cigarettes (EC) could help people with COPD reduce the harm of combustible cigarettes (CC) through reductions in number of Cigarettes per Day (CPD) or quitting CC completely. The purpose of this pilot study is to identify barriers and facilitators to the use of and assess the preliminary effectiveness of EC as a harm reduction strategy among people with COPD. Methods In an open-label two-arm randomized controlled trial pilot study, 60 patients identified as smokers with a COPD diagnosis via electronic health records from a large urban health center are randomized in a 1:1 ratio to either standard care [counseling + nicotine replacement therapy (NRT)] or counseling + EC. The NRT arm will receive nicotine patches and nicotine lozenges for 12 weeks. The EC arm will receive EC for 12 weeks. Both cohorts will receive counseling from a licensed mental health counselor. Using ecological momentary assessment, participants will report their use of CC in both arms and EC use in the EC arm daily via text message. Primary outcomes will be feasibility and acceptability of intervention, and secondary outcomes will be reduction in CPD and change in COPD symptoms as measured by COPD Assessment Tool (CAT) score at 12-weeks. EC displacement of CC. To explore attitudes towards the use of EC as a harm-reduction strategy for patients with COPD, interviews will be performed with a sample of participants from both study arms. Discussion Despite decades of availability of smoking cessation medications, nearly half of people with COPD still smoke. This study aims to address the unmet need for feasible and effective strategies for reducing CC use among those with COPD, which has the potential to significantly improve the health of people with COPD who smoke. Trial Registration ClinicalTrials.gov Identifier: NCT04465318.

Background Late-onset Pompe disease (LOPD) is a rare, metabolic disease primarily affecting the musculoskeletal and respiratory systems. Forced vital capacity (FVC) is commonly used to measure pulmonary function; however, associations between FVC and other LOPD outcomes remain unclear. Methods A systematic literature review was conducted on November 2015, updated September 2016 and supplemented with clinical trial data from the sponsor. Outcomes included: 6-min walk test distance (6MWT), FVC, maximal inspiratory/expiratory pressure (MIP/MEP), Medical Research Council-skeletal muscle strength score (MRC), 36-item short-form survey-physical component score (SF-36), Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS) and survival. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes. Results Fifteen studies were selected. From cross-sectional analyses, FVC and MRC were most strongly associated. Specifically, patients with 10% higher FVC (a round number for illustrative purposes only) were associated with a 4.72% (95% confidence interval [CI]: 3.37, 6.07) higher MRC score, indicating a positive association. Similarly, slopes for the 6MWT and SF-36 relative to a 10% higher FVC were estimated at 33.2 meters (95% CI 24.0, 42.4) and 1.2% (95% CI 0.24, 2.16%), respectively. From longitudinal analyses, a 10% incremental increase in predicted FVC was associated with an average increase of 4.12% in MRC score (95% CI 1.29, 6.95), 35.6 m in the 6MWT (95% CI 19.9, 51.6), and 1.34% in SF-36 (95% CI 0.08, 2.60). There was insufficient data to conduct analyses for RHS, FSS and survival. Conclusions FVC is positively associated with LOPD measures and outcomes across multiple domains. Additionally, longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36. Electronic supplementary material The online version of this article (10.1007/s00415-019-09401-1) contains supplementary material, which is available to authorized users.

The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) released large amounts of toxic dusts and fumes into the air that exposed many community members who lived and/or worked in the local area. Many community members, defined as WTC survivors by the federal government, developed lower respiratory symptoms (LRS). We previously reported the persistence of these symptoms in patients with normal spirometry despite treatment with inhaled corticosteroids and/or long-acting bronchodilators. This report expands upon our study of this group with the goal to identify molecular markers associated with exposure and heterogeneity in WTC survivors with LRS using a selected plasma biomarker approach. Samples from WTC survivors with LRS (n = 73, WTCS) and samples from healthy control participants of the NYU Bellevue Asthma Registry (NYUBAR, n = 55) were compared. WTCS provided information regarding WTC dust exposure intensity. Hierarchical clustering of the linear biomarker data identified two clusters within WTCS and two clusters within NYUBAR controls. Comparison of the WTCS clusters showed that one cluster had significantly increased levels of circulating matrix metalloproteinases (MMP1, 2, 3, 8, 12, 13), soluble inflammatory receptors (receptor for advanced glycation end-products-RAGE, Interleukin-1 receptor antagonist (IL-1RA), suppression of tumorigenicity (ST)2, triggering receptor expressed on myeloid cells (TREM)1, IL-6Ra, tumor necrosis factor (TNF)RI, TNFRII), and chemokines (IL-8, CC chemokine ligand- CCL17). Furthermore, this WTCS cluster was associated with WTC exposure variables, ash at work, and the participant category workers; but not with the exposure variable WTC dust cloud at 9/11. A comparison of WTC exposure categorial variables identified that chemokines (CCL17, CCL11), circulating receptors (RAGE, TREM1), MMPs (MMP3, MMP12), and vascular markers (Angiogenin, vascular cell adhesion molecule-VCAM1) significantly increased in the more exposed groups. Circulating biomarkers of remodeling and inflammation identified clusters within WTCS and were associated with WTC exposure.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention—the starting point for delivery of “All the right care, but only the right care,” an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

This study derives normative prediction equations for respiratory impedance in a healthy asymptomatic urban population using an impulse oscillation system (IOS). In addition, this study uses body mass index (BMI) in the equations to describe the effect of obesity on respiratory impedance. Data from an urban population comprising 472 healthy asymptomatic subjects that resided or worked in lower Manhattan, New York City were retrospectively analysed. This population was the control group from a previously completed case–control study of the health effects of exposure to World Trade Center dust. Since all subjects underwent spirometry and oscillometry, these previously collected data allowed a unique opportunity to derive normative prediction equations for oscillometry in an urban, lifetime non-smoking, asymptomatic population without underlying respiratory disease. Normative prediction equations for men and women were successfully developed for a broad range of respiratory oscillometry variables with narrow confidence bands. Models that used BMI as an independent predictor of oscillometry variables (in addition to age and height) demonstrated equivalent or better fit when compared with models that used weight. With increasing BMI, resistance and reactance increased compatible with lung and airway compression from mass loading. This study represents the largest cohort of healthy urban subjects assessed with an IOS device. Normative prediction equations were derived that should facilitate application of IOS in the clinical setting. In addition, the data suggest that modelling of lung function may be best performed using height and BMI as independent variables rather than the traditional approach of using height and weight., Prediction equations for respiratory impedance were derived in an urban cohort incorporating the effects of mass loading from obesity. Urban exposures had minimal effect on impedance allowing application of the equations to a broad range of populations. https://bit.ly/3a3zZvd

Summary Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov , NCT02782741 . We report results of the 49-week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Funding Sanofi Genzyme.

Background: The characteristics of community members exposed to World Trade Center (WTC) dust and fumes with Chronic Obstructive Pulmonary Disease (COPD) can provide insight into mechanisms of airflow obstruction in response to an environmental insult, with potential implications for interventions. Methods: We performed a baseline assessment of respiratory symptoms, spirometry, small airway lung function measures using respiratory impulse oscillometry (IOS), and blood biomarkers. COPD was defined by the 2019 GOLD criteria for COPD. Patients in the WTC Environmental Health Center with

The destruction of the World Trade Center (WTC) towers on the 11th of September, 2001 released a vast amount of aerosolized dust and smoke resulting in acute and chronic exposures to community members as well as responders. The WTC Environmental Health Center (WTC EHC) is a surveillance and treatment program for a diverse population of community members, including local residents and local workers with WTC dust exposure. Many of these patients have reported persistent lower respiratory symptoms (LRS) despite treatment for presumed asthma. Our goal was to identify conditions associated with persistent uncontrolled LRS despite standard asthma management. We recruited 60 patients who were uncontrolled at enrollment and, after a three-month run-in period on high-dose inhaled corticosteroid and long acting bronchodilator, reassessed their status as Uncontrolled or Controlled based on a score from the Asthma Control Test (ACT). Despite this treatment, only 11 participants (18%) gained Controlled status as defined by the ACT. We compared conditions associated with Uncontrolled and Controlled status. Those with Uncontrolled symptoms had higher rates of upper airway symptoms. Many patients had persistent bronchial hyper-reactivity (BHR) and upper airway hyper-reactivity as measured by paradoxical vocal fold movement (PVFM). We found a significant increasing trend in the percentage of Controlled with respect to the presence of BHR and PVFM. We were unable to identify significant differences in lung function or inflammatory markers in this small group. Our findings suggest persistent upper and lower airway hyper-reactivity that may respond to standard asthma treatment, whereas others with persistent LRS necessitate additional diagnostic evaluation, including a focus on the upper airway.

Supplemental Digital Content is available in the text., Objectives: Mortality rates in intubated coronavirus disease 2019 patients remain markedly elevated. Some patients develop sudden refractory hypercapnia and hypoxemia not explained by worsening pulmonary parenchymal disease. This case series highlights clinical findings and management of coronavirus disease 2019 patients with refractory hypercapnia despite maximal/optimal ventilatory support. Hypercapnia could not be explained by worsening lung disease or other common factors, and thus, a pulmonary vascular etiology was suggested. The pillars of management were targeted to improve pulmonary vascular patency via aggressive anticoagulation and support right ventricular function. Data Sources: Four consecutive patients with confirmed coronavirus disease 2019 infection with sudden hypercapnia and hypoxemia were included. Data Synthesis: There was sequential development of: 1) severe hypercapnia attributable to marked elevation of dead space without radiographic changes; 2) concomitant coagulopathy manifest by an increase in d-dimer levels; 3) progressive shunt with consequent hypoxemia; and 4) right ventricular dysfunction. Management included extracorporeal Co2 removal, direct thrombin inhibition, pulmonary vasodilators, and inotropic support. Marked improvement in Pao2 allowed reduction in Fio2 in all patients, extracorporeal Co2 removal was discontinued in three patients over the ensuing 3 weeks, and one patient was discharged home. Conclusions: We speculate that thromboinflammation with pulmonary microvasculature occlusion leads to a sudden increase in dead space and shunt resulting in severe hypercapnia and hypoxemia in coronavirus disease 2019 patients. Early identification of these physiologic and clinical biomarkers could trigger the institution of therapies aiming to reverse the hypercoagulable state and support right ventricular function.

Oscillometry (also known as the forced oscillation technique) measures the mechanical properties of the respiratory system (upper and intrathoracic airways, lung tissue and chest wall) during quiet tidal breathing, by the application of an oscillating pressure signal (input or forcing signal), most commonly at the mouth. With increased clinical and research use, it is critical that all technical details of the hardware design, signal processing and analyses, and testing protocols are transparent and clearly reported to allow standardisation, comparison and replication of clinical and research studies. Because of this need, an update of the 2003 European Respiratory Society (ERS) technical standards document was produced by an ERS task force of experts who are active in clinical oscillometry research.The aim of the task force was to provide technical recommendations regarding oscillometry measurement including hardware, software, testing protocols and quality control.The main changes in this update, compared with the 2003 ERS task force document are 1) new quality control procedures which reflect use of “within-breath” analysis, and methods of handling artefacts; 2) recommendation to disclose signal processing, quality control, artefact handling and breathing protocols (e.g.number and duration of acquisitions) in reports and publications to allow comparability and replication between devices and laboratories; 3) a summary review of new data to support threshold values for bronchodilator and bronchial challenge tests; and 4) updated list of predicted impedance values in adults and children.

Obesity hypoventilation syndrome (OHS) is defined as chronic hypercapnia during wakefulness in obese subjects not attributable to underlying respiratory disease. This syndrome is associated with pulmonary hypertension and right ventricular dysfunction that occurs on a background of the central circulatory congestion described in obesity. The role of sleep-disordered breathing in OHS was not recognized initially since the obstructive sleep apnea syndrome was not described until many years after initial recognition of OHS. Nevertheless, it has since been demonstrated that resolution of obstructive apnea and hypopnea and/or central hypoventilation with positive airway pressure therapy corrects the cardiorespiratory failure with normalization of acid-base balance. 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 for the evolution of OHS integrating whole-body CO2 kinetics, respiratory-renal interaction, and alterations in respiratory control is presented in the following review.

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 FEV1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV1/FVC ratio 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.

Diagnosis of asthma in obese individuals frequently relies on clinical history, as airflow by spirometry may remain normal. This study hypothesised that obese subjects with self-reported asthma and normal spirometry will demonstrate distinct clinical characteristics, metabolic comorbidities and enhanced small airway dysfunction as compared with healthy obese subjects. Spirometry, plethysmography and oscillometry data pre/post-bronchodilator were obtained in 357 obese subjects in three groups as follows: no asthma group (n=180), self-reported asthma normal spirometry group (n=126), and asthma obstructed spirometry group (n=51). To assess the effects of obesity related to reduced lung volume, oscillometry measurements were repeated during a voluntary inflation to predicted functional residual capacity (FRC). Dyspnoea was equally prevalent in all groups. In contrast, cough, wheeze and metabolic comorbidities were more frequent in the asthma normal spirometry and asthma obstructed spirometry groups versus the no asthma group (p, Obese subjects with self-reported asthma have exaggerated small airway dysfunction even when spirometric airflow is normal. Cough and wheeze are associated with metabolic comorbidities providing a milieu with impact on small airway function. https://bit.ly/2VFrA9O

The effects of childhood exposure to perfluoroalkyl substances (PFASs) on lung function remain mostly unknown. Previous research indicates that children living or going to school near the World Trade Center (WTC) disaster were exposed to high levels of PFASs, among other toxic chemicals. To explore the effects of PFAS exposure on lung function, we measured serum PFASs in a cohort of children from the WTC Health Registry and a matched control group. Perfluorooctanesulfonate had the highest median concentrations in both groups (WTCHR = 3.72 ng/mL, Comparison = 2.75 ng/mL), while the lowest median concentrations were seen for perfluoroundecanoic acid (WTCHR = 0.12 ng/mL, Comparison = 0.01 ng/mL). Lung function outcomes were measured by spirometry, plethysmography, and oscillometry. Asthma diagnosis and serum eosinophil count were also recorded. We examined the relationships of each PFAS with lung function parameters and eosinophil count using linear regressions. Odds ratios for asthma were obtained for each PFAS using logistic regression. The effect of total PFASs on these outcomes was also assessed. All regression models were adjusted for sex, race/ethnicity, age, body mass index (BMI) and tobacco smoke exposure. We found that serum PFASs were not statistically associated with the measured lung function parameters, asthma diagnosis, or eosinophil count in this cohort (p < 0.05). These findings highlight the need for more longitudinal studies to explore the long-term effects of childhood PFAS exposure on lung function past adolescence and early adulthood.

Smoking induced inflammation leads to distal airway destruction. However, the relationship between distal airway dysfunction and inflammation remains unclear, particularly in smokers prior to the development of airway obstruction. Seven normal controls and 16 smokers without chronic obstructive pulmonary disease (COPD) were studied. Respiratory function was assessed using the forced oscillation technique (FOT). Abnormal FOT was defined as elevated resistance at 5 Hz (R5). Parameters reflecting distal lung function included frequency dependence of resistance (R5–20) and dynamic elastance (X5). Inflammation was quantified in concentrated bronchoalveolar lavage utilising cell count differential and cytokines expressed as concentration per mL epithelial lining fluid. All control subjects and seven smokers had normal R5. Nine smokers had elevated R5 with abnormal R5–20 and X5, indicating distal lung dysfunction. The presence of abnormal FOT was associated with two-fold higher lymphocyte and neutrophil counts (p0.47, p, Isolated dysfunction in distal airways identifies pulmonary inflammation in asymptomatic smokers with normal airflow http://ow.ly/8bVk305aVkj

Objective Longitudinal assessment of lower respiratory symptoms (LRS) in community members with World Trade Center (WTC) exposures. Methods Adult members of a treatment program with complete standardized visits were evaluated (n = 798). Association of demographic characteristics, mental health symptoms and lung function with trajectory of LRS between initial and monitoring visit was evaluated. Results Severe LRS were present in 70% at initial and 63% at monitoring visit. Initial severe LRS were associated with WTC dust cloud exposure and mental health symptoms. Spirometry measures were not associated with LRS severity or trajectory; improvement in LRS was associated with improved lung function measured with forced oscillometry techniques. Conclusion Many community patients in a WTC treatment program had severe LRS associated with exposures and mental health symptoms. Improvement in LRS was associated with improvement in measures of small airway function. Am. J. Ind. Med. 59:777–787, 2016. © 2016 Wiley Periodicals, Inc.

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 ( 0.001 vs. baseline). The dose–response of FOT (reactivity) was greater compared with subjects that remained asymptomatic (P

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

In patients with Late-Onset Pompe Disease (LOPD), progressive respiratory muscle involvement leads to reduced pulmonary function, with respiratory failure the most common cause of mortality. Early disease manifestations include sleep-disordered breathing, which can be treated with non-invasive ventilation; however, progressive diurnal deficits can require invasive ventilation. To determine if pulmonary function tests (PFTs) predict the thresholds for ventilation and wheelchair use, a systematic literature review identified cross-sectional clinical patient data (N = 174) that was classified into ventilation and wheelchair cohorts. PFTs included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and vital capacity (VC), with vital capacities measured in the upright (-U) and supine (-S) positions. Receiver operating characteristic (ROC) curves were used to calculate cut-points (CP) and area under the curve (AUC). For all ventilation and mobility thresholds tested, ROC analyses demonstrated AUC values from 86–89% for MIP, 72–96% for MEP, and 74–96% for all vital capacity metrics. Thus, PFTs are useful in predicting the thresholds for nighttime ventilation, daytime ventilation, and wheelchair use, with MIP and VC-U having both high AUC values and consistency. The PFT mobility CPs were low (MIP CP = 0.9 kPa, MEP, CP = 2.6 kPa, VC-U CP = 19% predicted), suggesting an endurance component associated with wheelchair use.

Following publication of this article, the authors noticed an error in Supplementary Table 1. In the original Supplementary Table 1, one of the criteria for control participants was incorrectly given as ‘Report extensive recent symptoms of depression: less than 14 on summed response (where “not at all” = 1 and “nearly every day” = 4) to recent’. This has now been corrected to: ‘Report extensive recent symptoms of depression: less than 5 on summed response (where “not at all” = 1 and “nearly every day” = 4) to recent’.

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: The study included 2,137 WTC-exposed firefighters who received a clinically-indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001–9/10/2017. A post-BD FEV(1) increase of >12% and 200 ml from baseline defined asthma, and post-BD FEV(1)/FVC ratio

The role for direct assessment of small airway function in subjects with respiratory symptoms but normal airflow by spirometry is discussed. Small airway disease syndrome is described in numerous disease states using a multidisciplinary approach. Data demonstrate that small airway disease is related to presence of respiratory symptoms, exposure to inhaled toxins, presence of local and systemic inflammation, and presence of histologic abnormalities within the distal lung. Investigation of immunological derangements associated with distal airway dysfunction in the setting of normal spirometry may provide insight into pathophysiological mechanisms that are present at disease onset. For the purposes of this symposium, data were reviewed in selected clinical conditions (obesity, environmental inhalational injury, and cigarette smoking) that have been recently studied in the Andre Cournand Pulmonary Physiology Laboratory at Bellevue Hospital using the forced oscillation technique.