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Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV.We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DWe identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV groupIsolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.

BACKGROUND: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. METHODS: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02–1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. RESULTS: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02–1 μm) concentrations decreased 77%–91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). CONCLUSIONS: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyper-responsiveness. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb substantially reduced expelled particles during MCT. Our aim was to evaluate whether this modification affects the delivered dose of methacholine.A mechanical ventilator was connected to a lung simulator with breathing frequency 15 breaths/min, tidal volume 500 mL, inspiratory-expiratory ratio 1:1, with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson Micro Mist or AeroEclipse II BAN nebulizers powered by either a dry gas source or a compressor system. A filter placed in line between the nebulizer and test lung was weighed before and after 1 min of nebulized methacholine delivery. Mean inhaled mass was measured with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles5 μm) and inhalation time. UnpairedThe addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using a 50-psi dry gas source, dose delivered with or without a viral filter did not differ with the Hudson (422.3 μg vs 282.0 μg,The addition of a viral filter to the nebulizer exhalation limb did not affect methacholine dose during bronchoprovocation testing. Routine use of a viral filter should be considered to improve pulmonary function technician safety and infection control measures during the ongoing COVID-19 pandemic.

BACKGROUND: Peak flow testing is a common procedure performed in ambulatory care. There are currently no data regarding aerosol generation during this procedure. Given the ongoing debate regarding the potential for aerosol transmission of SARS-CoV-2, we aimed to quantify and characterize aerosol generation during peak flow testing. METHODS: Five healthy volunteers performed peak flow maneuvers in a particle-free laboratory space. Two devices continuously sampled the ambient air during the procedure. One device can detect ultrafine particles 0.02–1 μm in diameter, while the second device can detect particles 0.3, 0.5, 1.0, 2.0, 5.0, and 10 μm in diameter. Five different peak flow meters were compared to ambient baseline during masked and unmasked tidal breathing. RESULTS: Ultrafine particles (0.02–1 μm) were generated during peak flow measurement. There was no significant difference in ultrafine particle mean concentration between peak flow meters (P = .23): Respironics (1.25 ± 0.47 particles/mL), Philips (3.06 ± 1.22), Clement Clarke (3.55 ± 1.22 particles/mL), Respironics Low Range (3.50 ± 1.52 particles/mL), and Monaghan (3.78 ± 1.31 particles/mL). Ultrafine particle mean concentration with peak flow testing was significantly higher than masked (0.22 ± 0.29 particles/mL) and unmasked tidal breathing (0.15 ± 0.18 particles/mL, P = .01), but the ultrafine particle concentrations were small compared to ambient particle concentrations in a pulmonary function testing room (89.9 ± 8.95 particles/mL). CONCLUSIONS: In this study, aerosol generation was present during peak flow testing, but concentrations were small compared to the background particle concentration in the ambient clinical environment. Surgical masks and eye protection are likely sufficient infection control measures during peak expiratory flow testing in asymptomatic patients with well controlled respiratory symptoms, but COVID-19 testing remains prudent in patients with acute respiratory symptoms prior to evaluation and peak expiratory flow assessment while the community prevalence of SARS-CoV-2 cases remains high.

BACKGROUND: The clinical benefits of cardiopulmonary rehabilitation are extensive, including improvements in health-related quality of life, emotional condition, physical function, and overall mortality. The COVID-19 pandemic continues to have a negative impact on center-based cardiopulmonary rehabilitation. Justifiable concern exists that the exercise-related increase in pulmonary ventilation within the rehabilitation classes may lead to the generation of infectious respiratory particles. RESEARCH QUESTION: Is cardiopulmonary rehabilitation while wearing a procedural mask a particle-generating procedure? STUDY DESIGN AND METHODS: Data were collected prospectively at a cardiopulmonary rehabilitation facility with all patients wearing a procedural mask. Small (0.3-4.9 µm) and large (5-10 µm) particle generation was quantified using a light-scattering particle counter. Data were analyzed by time, exertion level, and number of participants. RESULTS: A total of 24 distinct patients attended two or more of the cardiopulmonary rehabilitation classes tested. Most of the patients were men (n = 16 [67%]) and were in rehabilitation because of cardiac disease. During the cardiopulmonary rehabilitation class, small and large micrometer-size particles increased with increasing class size. In classes with four patients or more, a significant increase was found from ambient levels in both small (four patients, P < .01; and five patients, P < .01) and large (four patients, P < .01; and five patients, P < .01) particle count that peaked at about 35 to 40 min during each class. INTERPRETATION: Using an airborne particle counter, we found significant exercise-related increases in both small and large micrometer-size particle generation during cardiopulmonary rehabilitation classes, with larger class sizes (ie, more patients), despite participants wearing a procedural mask.

Background Patients discharged following admissions for acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) frequently require unplanned readmissions, increasing costs and morbidity for thousands of patients suffering from COPD. The Hospital Readmissions Reduction Program provided financial incentives to reduce 30-day readmissions for AE-COPD, but although risk factors for readmission are known, few evidence-based interventions achieve this goal. Members of the Mayo Clinic Care Network (MCCN) formed a collaborative to seek ways to reduce 30-day readmission for patients admitted with AE-COPD. Methods Seventeen MCCN organizations participated in an improvement collaborative in 2016 and 2017. Mayo Clinic subject matter experts shared improvement webinars, protocols, and educational materials related to AE-COPD and delivered individualized coaching to facilitate improvement at each site over a six-month engagement. Among other recommended interventions, organizations worked to increase the proportion of COPD patients who had a standardized disease severity staging during admission, inhaler appropriateness evaluations, a COPD treatment action plan, and clinical contact at Results Same-hospital readmission rates improved from 17.7% ± 3.6 to 14.5% ± 4.0 (weighted difference −4.38, p = 0.008, paired t-test). In addition, participating teams stated that the collaborative framework helped them develop strategies that improved patient care and organizational capacity for improvement in other domains. Conclusion The collaborative framework, beginning with education delivered in person and via webinars, combined with telephonically delivered coaching and knowledge sharing, assisted most members to improve care. Fourteen of 17 participating sites experienced a reduced AE-COPD readmission rate.

To determine the efficacy of IL-5 inhibitory therapy in severe, refractory asthma in a real-world clinical setting from a tertiary referral center.A retrospective chart review of patients with severe asthma treated with IL-5 biologic therapy for ≥ 6 months at Mayo Clinic in Rochester, Minnesota between January 1, 2013 and August 31, 2019.Over the study period, we identified 63 patients with a mean age of 54 who received an IL-5 inhibitor for ≥ 6 months. A total of 55 patients received mepolizumab, 2 received benralizumab, and 9 patients received both. Patients were followed up for a mean of 25 months. The mean number of months of oral prednisone use prior to biologic initiation was 64. There was a significant reduction in the median dose of prednisone in the 24 months after drug initiation (15 mg vs. 0 mg; p = 0.0001). Similarly; there was a significant decline in the median number of asthma exacerbations in the 24 months before and after drug initiation (7 vs. 2; p = 0.0001). The mean number of emergency room (ER) visits and hospitalizations decreased from 5.1 and 2.0 to 1.6 and 0.4 in the 24 months before and after therapy initiation (p 0.0001 and p = 0.007, respectively) CONCLUSIONS: IL-5 inhibitory therapy is associated with significant and long-term sustained reductions in asthma exacerbation frequency, ER visits, hospitalizations, as well as oral steroid usage in a patient population with refractory steroid-dependent asthma referred to a tertiary referral center.

Background Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. Methods This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough ≥ 8 weeks' duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. Results Eight randomized controlled trials and two case series (≥ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma-related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma-associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. Conclusions The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease.

TOPIC: Respiratory Care TYPE: Original Investigations PURPOSE: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyperresponsiveness. Current ERS guidelines recommend that measures should be taken to minimize technician exposure to methacholine aerosol, with added infection control concerns in the context of the ongoing COVID-19 pandemic. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb reduced expelled particle concentrations by 77-91% during MCT. Our aim was to evaluate whether this modification resulted in a change in the delivered dose of methacholine. METHODS: Following published industry testing standards for MCT, we connected a Hamilton-G5 mechanical ventilator and Michigan lung simulator in series with respiratory rate 15 breaths/min, tidal volume (VT) 500 mL, I:E ratio 1:1 with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson MicroMist and AeroEclipse II BAN nebulizers powered by either a dry gas source at 50 psi and 4.5 L/min or the Ombra compressor system, in addition to our current MCT protocol which utilizes Hudson MicroMist nebulizer with KoKo dosimeter (3 breaths). A filter placed in line between the nebulizer and test lung was weighed before and after 1 minute of nebulized methacholine delivery. Mean inhaled mass was calculated from three trials of each method with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 µm) and inhalation time. Unpaired t-test was used to compare methacholine dose delivery with and without viral filter placement. Due to multiple independent comparisons, Bonferroni correction was used and alpha level was set at 0.01. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using the 50 psi dry gas source, dose delivered with the Hudson MicroMist did not differ with (461.0 µg) or without (307.8 µg) a viral filter (P=0.11) or with the AeroEclipse II BAN with (580.8 µg) or without (678.4) a viral filter (P=0.59). Using the Ombra compressor, dose delivered with the Hudson MicroMist did not differ with (1063.3 µg) or without (947.5 µg) a viral filter (P=0.026) or with AeroEclipse II BAN with (843.8 µg) or without (648.3) viral filter (P=0.42). Dose delivery did not differ significantly when using the KoKo dosimeter and Hudson MicroMist with or without a viral filter (P=0.20) using a 3-breath protocol. CONCLUSIONS: The addition of a viral filter to the nebulizer expiratory limb did not result in a significant change in the in the delivered dose of methacholine. CLINICAL IMPLICATIONS: Based on these findings, use of a viral filter to limit the concentration of expelled aerosol during MCT should be considered to improve pulmonary function technician safety and potentially reduce the risk of infectious exposure during the ongoing COVID-19 pandemic. DISCLOSURES: No relevant relationships by Kaiser Lim, source=Web Response no disclosure submitted for todd meyer;No relevant relationships by Alexander Niven, source=Web Response No relevant relationships by Paul Scanlon, source=Web Response No relevant relationships by Yosuf Subat, source=Web Response No relevant relationships by Keith Torgerud, source=Web Response

Chyloptysis is a rare clinical presentation. Diagnosis is challenging and requires recognition of milky-sputum or bronchial casts. We describe a case of chyloptysis secondary to thoracic lymphangiectasia that necessitated surgical ligation of the main thoracic duct and accessory branches. The patient had no postoperative complications, and at 6-month follow-up remained symptom-free. A paucity of literature describes the management of chyloptysis. We review diagnosis, treatment considerations and operative principles.

Background & Aims Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE. Methods For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0–100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8). Results The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0–6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from –4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11). Conclusion Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT 01386112

Background The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices. Methods This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model. Results The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance. Conclusion Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.

Background Acute respiratory worsening (ARW) requiring hospitalization in patients with fibrotic interstitial lung disease (f-ILD) is common. Little is known about the frequency and implications of ARW in IPF and non-IPF ILD patients hospitalized for acute exacerbation (AE) vs known causes of ARW. Methods All consecutive patients with f-ILD hospitalized with ARW at our institution from 2000 to 2014 were reviewed. ARW was defined as any worsening of respiratory symptoms with new or worsened hypoxemia or hypercapnia within 30 days of admission. Suspected AE was defined using modified 2007 American Thoracic Society/European Respiratory Society criteria. Known causes of ARW were reviewed and collated along with in-hospital and all-cause mortality postdischarge. Results A total of 220 patients (100 with IPF and 120 non-IPF) composed 311 admissions for ARW. Suspected AE (SAE) comprised 52% of ARW admissions, followed by infection (20%), and subacute progression of disease (15%). In-hospital mortality was similar in patients with IPF vs patients without (55 vs 45%, P = .18), but worse in suspected AE admission types (OR, 3.1 [1.9-5.14]). One-year survival after last ARW admission for the whole cohort was 22%, despite only 27% of patients presenting with baseline oxygen requirement at admission and a mean admission Charlson Comorbidity Index score of 5.4 (expected 1-year survival, 89%). Survival after discharge was similar between SAE and secondary ARW admission types in both IPF and non-IPF patients. Conclusions Among patients with f-ILD, hospitalization for ARW appears associated with significant in-hospital and postdischarge mortality regardless of underlying fibrotic lung disease or non-AE cause of acute respiratory decline.

Chronic cough is the most common reason for medical office visits in the United States. The typical patient has coughed more than 8 years and seen many specialists. This quality improvement project is an ambulatory clinic redesign to deliver efficient, patient-centered care with interspecialty collaboration. Methodology included the Institute for Healthcare Improvement collaborative model focused on Lean/Six Sigma and ADKAR (Awareness, Desire, Knowledge, Ability, Reinforcement) Change Management. Interventions targeted education to referring providers, implementation of software changes, building a collaborative interdepartmental scheduling decision tree, and an interclinic dashboard enhancing communication and decision support. Outcome measures compare group resource utilization, evidenced by the total number of specialist referrals for same indication of chronic cough (International Classification of Diseases, Ninth Revision: 786.2), and length of time to complete evaluation. A retrospective review of 165 medical records yielded 2 groups, "current care" (n = 67) and "intervention" (n = 68). The number of specialist referrals per patient was reduced in the intervention group (M = 1.22, SD = 0.48) compared with the current care group (M = 3.33, SD = 1.02). Length of itinerary was reduced in the intervention group (M = 11.90, SD = 12.13, GM = 6.82) compared with the current care group (M = 126.93, SD = 158.13, GM = 54.8). Multidisciplinary collaboration, communication, coordinating diagnosis, and management of multifactorial conditions, such as chronic cough, are associated with lower costs and decreased utilization of health care resources.

Background Acute interstitial nephritis (AIN) presents with acute kidney injury, with evidence of interstitial inflammation and tubulitis on histology, and the presence of fever, rash, and eosinophiluria. Although the pathogenesis of this disease is not well understood, cell-mediated immunity is thought to play a major role. We hypothesized that IgE mediated mast cell activation is also involved in the pathogenesis of renal injury in AIN. Methods 28 patients, with biopsy proven AIN over a 5-year period, were included in this study. Clinical data, including renal outcomes and the etiologies of AIN, were evaluated in all patients. Available tissues (renal biopsy) from 26 of the patients were stained for β-tryptase (marker for mast cell degranulation), IgE, IL-16, and CD3. A negative control for immunostaining was included. Results Samples from all 26 individuals stained positive for β-tryptase (mean of 11.16 cells/high power field), IgE (mean average of 0.68 cells/HPF), IL-16 (28% of the interstitium), and CD3 (33% of the interstitium). Acute interstitial nephritis was due to medication in 73%, systemic disease in 15%, and unknown (idiopathic) in 12% of the cases. 86% of patients were treated with corticosteroids. 18% required acute inpatient dialysis, with 7% remaining on dialysis longterm. Conclusions Our study suggests that IgE and mast cell activation may play a role in the pathogenesis of AIN.

Bronchial thermoplasty (BT) is the first nonpharmacologic interventional therapy approved by the U.S. Food and Drug Administration in 2010 for severe asthma. This approval was based on randomized sham-controlled trial called Asthma Intervention Research (AIR) 2 published in 2010. BT involves the application of radiofrequency energy to airways with an aim to selectively ablate airway smooth muscle. BT is currently marketed for patients with "severe" asthma. Most practicing clinicians apply this severity category to patients with oral corticosteroid dependence, frequent exacerbations, or a significantly reduced forced expiratory volume in 1 second along with a poor quality of life. Did the patients studied in the AIR-2 trial have these clinical features? Was there a reduction in severe asthma exacerbation achieved in the intervention group? Did any of the primary or secondary end points in the AIR-2 trial show a positive signal? There continues to be controversy regarding patient selection and primary outcome. Its efficacy in the management of the patient with difficult-to-manage asthma is uncertain. This review covered pertinent aspects of BT, the design and results of the AIR-2 trial, and provides the practicing allergist with a comprehensive overview of this therapy.

Background : Chronic rhinosinusitis (CRS) is important in asthma and chronic cough assessment. An accurate diagnosis of CRS based solely on symptoms and nasal endoscopy can be difficult. Sinus CT-imaging is usually recommended in patients with negative rhinoscopy. Nasal nitric oxide (nNO) levels obtained passively and while humming are decreased in sinusitis due to ostiomeatal complex blockage of paranasal sinus gas exchange by inflamed tissue. A nNO measurement is a potential point-of-care test (POCT) for CRS. The SinoNasal Outcome Test (SNOT-20) is a clinical tool to assess symptoms in CRS. Objective : To evaluate if nNO levels provided objective information about CRS that would correlate with individual elements in the SNOT-20 and 6 additional CRS related symptoms. To examine these 26 symptom parameters for related clusters, and test correlation of the clusters with nNO measurements. Methods : In 180 patients, basal and humming nNO level measurements, and 26 symptoms (SNOT-20 plus 6 added items) were collected. Hierarchical cluster analysis was applied to sort the data into clusters. Results : The 26 questions grouped into 5 different clusters. 2 clusters contained questions that were most disease specific for sinonasal diseases in patients referred for subspecialty asthma and chronic cough evaluation. We demonstrated that nNO levels during humming, and the ratio between humming and basal nNO, correlated best with clusters 2 and 4. Conclusion : Baseline and humming nNO measurements provide objective information about CRS. nNO measurements offers the potential of a POCT for objective assessment of CRS in patients presenting to a pulmonary clinic.

We highlight a rare presentation of Legionella infection in a 77-year-old woman with a clinical diagnosis of giant cell arteritis 2 months prior to presentation. She was started on 60 mg prednisone that was tapered to 10 mg after 4 weeks following her diagnosis. She presented with a 1-month progressive dyspnoea in the absence of any other symptoms. Her exposure history was significant only for a recent trip to Florida where she stayed at a hotel. Initial laboratory workup was significant for hyponatraemia (127 mmol/L). Workup including bronchoalveolar lavage (BAL) and induced sputum for gram stain, acid fast stain and bacterial culture were negative for Pneumocystis jirovecii pneumonia and other opportunistic infectious agents. However, BAL was positive for Legionella pneumophila via PCR that was confirmed by a positive urinary Legionella antigen. The patient received treatment with levofloxacin that led to full resolution of her symptoms.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease.

This overview will demonstrate that cough is a common and potentially expensive health-care problem. Improvement in the quality of care of those with cough has been the focus of study for a variety of disciplines in medicine. The purpose of the Cough Guideline and Expert Panel is to synthesize current knowledge in a form that will aid clinical decision-making for the diagnosis and management of cough across disciplines and also identify gaps in knowledge and treatment options.

BACKGROUND Electromyographic evaluation of diaphragmatic neuromuscular disease in patients with COPD is technically difficult and potentially high risk. Defining standard values for diaphragm thickness and thickening ratio using B-mode ultrasound may provide a simpler, safer means of evaluating these patients. METHODS Fifty patients with a diagnosis of COPD and FEV 1 RESULTS There was no significant difference in diaphragm thickness or thickening ratio between sides within groups (control subjects or patients with COPD) or between groups, with the exception of the subgroup with severe air trapping (residual volume > 200%), in which the only difference was that the thickening ratio was higher on the left ( P = .0045). CONCLUSIONS In patients with COPD presenting for evaluation of coexisting neuromuscular respiratory weakness, the same values established for healthy control subjects serve as the baseline for comparison. This knowledge expands the role of ultrasound in evaluating neuromuscular disease in patients with COPD.

Bronchial thermoplasty (BT) involves the application of radiofrequency energy to visible proximal airways to selectively ablate airway smooth muscle. BT is the first nonpharmacologic interventional therapy approved by the US Food and Drug Administration (FDA) for severe asthma. This approval was based on the results of the pivotal Asthma Intervention Research (AIR)-2 trial, which is the only randomized, double-blind, sham-controlled trial of BT. The primary end point of the AIR-2 trial was improvement in the Asthma Quality of Life Questionnaire (AQLQ). The results of the AIR-2 trial have generated enormous interest, controversy, and confusion regarding the true efficacy of BT for severe asthma. Current marketing of BT highlights its use for patients with "severe" asthma, which is interpreted by most practicing clinicians as meaning oral corticosteroid dependence, frequent exacerbations, or a significantly reduced FEV1 with a poor quality of life. Did the AIR-2 trial include patients with a low FEV1, oral steroid dependence, or frequent exacerbations? Did the trial show efficacy for any of the primary or secondary end points? The FDA approved the device based on the reduction in severe asthma exacerbations. However, were the rates of asthma exacerbations, ED visits, or hospitalizations truly different between the two groups, and was this type of analysis even justified given the original study design? This commentary is designed to specifically answer these questions and help the practicing clinician navigate the thermoplasty literature with confidence and clarity. We carefully dissect the design, conduct, and results of the AIR-2 trial and raise serious questions about the efficacy of bronchial thermoplasty.

Ipilimumab is a monoclonal antibody used in the treatment of unresectable or metastatic melanoma. Several immune-related adverse events including potential fatal events have been reported following its use. We report a case of a 66-year-old man who presented with severe acute exertional dyspnea and orthopnea following administration of ipilimumab for metastatic melanoma. Although various peripheral neuropathy syndromes associated with ipilimumab have been reported, bilateral phrenic nerve paralysis has not been previously reported. This case also highlights the clinical features of bilateral phrenic nerve neuropathy. Pulmonologists have to be aware of these unusual immune-related respiratory adverse events in patients being treated with monoclonal antibodies.

Background The long-term safety of patient-administered nebulized lidocaine for control of chronic cough has not been established. Methods We performed a retrospective study of adults who received a prescription and nurse education for nebulized lidocaine for chronic cough between 2002 and 2007. A survey questionnaire inquiring about adverse reactions and the effectiveness of nebulized lidocaine was developed and administered to these individuals after the nebulized lidocaine trial. We conducted two mailings and a postmailing phone follow-up to nonresponders. When adverse events were reported in the questionnaire response, a structured phone interview was conducted to obtain additional details. Results Of 165 eligible patients, 99 (60%) responded to the survey. Responders were a median age of 62 years (range, 29–87 years); 77 (79%) were women, and 80 (82%) were white. The median duration of cough was 5 years before treatment with nebulized lidocaine. Of the patients who used nebulized lidocaine (93% of survey responders), 43% reported an adverse event. However, none of these events required an emergency visit, hospitalization, or antibiotic therapy for aspiration pneumonia. The mean (SD) of the pretreatment cough severity score was 8.4 (1.6) and posttreatment was 5.9 (3.4) ( P Conclusions Adults tolerated self-administration of nebulized lidocaine for difficult-to-control chronic cough. No serious adverse effects occurred while providing symptomatic control in 49% of patients.

Importance Refractory chronic cough is a debilitating condition with limited therapeutic options. Laryngeal botulinum toxin type A (BtxA) has been anecdotally reported to benefit patients with chronic cough. We report on our experience with the use of BtxA for the treatment of patients with refractory chronic cough. Objective To describe the effects of electromyography (EMG)-guided thyroarytenoid (TA) BtxA injection for the treatment of refractory chronic cough. Design, Setting, and Participants For this single tertiary referral center retrospective case series, we included all patients with refractory chronic cough who received bilateral EMG-guided TA BtxA injections (n = 22) between July 1, 2013, and July 31, 2014, at the Mayo Clinic in Rochester, Minnesota. Intervention Bilateral TA BtxA injection. Main Outcomes and Measures The primary outcome is a self-reported improvement of 50% or more in cough severity and/or symptoms by a 2-month follow-up telephone call. Adverse events and patient-reported quality measures were also assessed. Results A total of 22 patients (median [interquartile range] age 61 [57.5-85] years; 19 of 22 women) underwent 31 distinct laryngeal BtxA treatment sessions. The primary outcome of self-reported improvement of 50% or more of cough severity and/or symptoms was achieved in 16 of 31 (52%) treatment sessions. Eleven patients (50%) reported greater than 50% improvement after the first BtxA injection. No major complications occurred. Postprocedural liquid dysphagia had a positive predictive value of 84% and negative predictive value of 100% for response to therapy. Conclusions and Relevance In this case series, laryngeal BtxA injection was well tolerated in patients with refractory chronic cough with half of participants experiencing at least short-term improvement in their cough. The occurrence of liquid dysphagia after a BtxA injection appeared to be predictive of a beneficial response. The durability of response, patient selection criteria, and optimal BtxA dosage remains to be determined.

Compared with methacholine challenge, exhaled nitric oxide is less expensive, is performed as a simpler point-of-care maneuver, and may provide treatment guiding information.To determine whether exhaled nitric oxide levels can predict the outcome of methacholine challenge in patients without obvious baseline obstruction.This retrospective database and medical record review included adults presenting to a tertiary care center from November 1, 2009, through August 31, 2013, who underwent methacholine challenge and exhaled nitric oxide measurement within 2 weeks of each other. Database extraction identified age, sex, body mass index, baseline corticosteroid use, testing indication, forced expiratory volume in 1 second (FEVA total of 1,322 individuals were identified, with 774 meeting the eligibility criteria. A total of 123 methacholine challenges (16%) had positive results. Fractional exhaled nitric oxide was statistically higher in those with positive methacholine challenge results (mean [SD], 41.9 [54.5] ppb vs 25.2 [19.7] ppb; P.01). Receiver operating characteristic curve revealed an area under the curve of 0.572 (P.01), suggesting a poor correlation between exhaled nitric oxide level and methacholine challenge outcome. Fractional exhaled nitric oxide of greater than 50 ppb has a sensitivity, specificity, positive predictive value, and negative predictive value of 12%, 89%, 17%, and 84%, respectively, for a positive methacholine challenge result.In this large, retrospective cohort of corticosteroid-naive pulmonary patients with normal FEV

Summary Background Patients with eosinophilic oesophagitis (EoE) commonly have asthma and atopy. Aims To determine the predictive factors of EoE in patients with asthma. Methods A retrospective analysis of a large database identified 156 asthma patients with EoE and 276 patients without EoE between 2000 and 2010. Clinical and laboratory characteristics were first analyzed in half of each group. Significant differences and modelling were then applied to the other half of each group in a split half analysis. Results Odds ratios and P-values found to predict the presence of EoE in asthma patients were: allergic vs. non-allergic asthma (4.07

Background The relationship between asthma controller medication use and exacerbation rates over time is unclear at the population level. Objective To estimate the change in asthma controller medication use between 2 time periods as measured by the controller-to-total asthma medication ratio and its association with changes in asthma exacerbation rates between 1997–1998 and 2004–2005. Methods The study design was a cross-sectional population-level comparison between individuals from 1997–1998 and 2004–2005. Study participants were individuals aged 5 to 56 years identified as having asthma in the Medical Expenditure Panel Survey (MEPS). The main outcome measures were a controller-to-total asthma medication ratio greater than 0.5 and asthma exacerbation rates (dispensing of systemic corticosteroid or emergency department visit/hospitalization for asthma) in 1997–1998 compared with 2004–2005. Results The proportion of individuals with a controller-to-total asthma medication ratio greater than 0.5, when adjusted for other demographic factors, has improved by 16.1% (95% CI: 10.8%, 21.3%) for all individuals from 1997–1998 to 2004–2005. Annual asthma exacerbation rates did not change significantly in any group from 1997–1998 to 2004–2005 (0.27/year to 0.23/year). African American and Hispanic individuals with asthma had higher asthma exacerbation rates and a lower proportion with a controller-to-total asthma medication ratio greater than 0.5 than whites in both 1997–1998 and 2004–2005; however, these differences were not statistically significant. Conclusions An increase in asthma controller-to-total medication ratio in a sample reflective of the US population was not associated with a decreased asthma exacerbation rate comparing 1997–1998 and 2004–2005.

Background The pathophysiology of upper airway cough syndrome is not well understood. Objective To investigate the levels of neuropeptides found in nasal mucus of subjects with and without the complaint of chronic cough. Methods Preformed nasal mucus from 26 subjects complaining of postnasal drip with chronic cough and 17 without self-reported chronic cough was collected at the time of presentation. The nasal secretions were assayed for 3 neuropeptides—substance P (SP), calcitonin gene-related peptide (CGRP), and Neurokinin A (NKA)—that have been previously linked to chronic cough. Results Coughing subjects with postnasal drip have significantly higher levels of CGRP and SP than noncoughing subjects with postnasal drip (69.0 ng vs 4.6 ng, P P = .004). The differences in NKA levels in nasal secretions between coughing and noncoughing subjects did not reach statistical significance (16.3 ng vs 3.4 ng, P = .067). Conclusions Both CGRP and SP levels are elevated in preformed nasal secretions of coughing subjects when compared with noncoughing subjects. Additional studies are needed to clarify whether CGRP and SP levels in preformed nasal secretions may assist in diagnosis or predicting treatment response in patients presenting with chronic cough.

Chronic cough is a common symptom-based diagnostic challenge for primary care physicians and respiratory specialists. Measurement of exhaled nitric oxide is a convenient, reproducible, and inexpensive point-of-service test. It can simplify the evaluation process of chronic cough by providing information regarding the state of airway inflammation. If exhaled nitric oxide is elevated, this is predictive of a favorable response to inhaled corticosteroids. This has the effect of reducing empirical trials for cough-variant asthma or eosinophilic bronchitis. The inclusion of exhaled nitric oxide in the diagnostic approach to chronic cough should be considered.

The new asthma guidelines have introduced impairment and risk assessments into the management of asthma. Impairment assessment is based on symptom frequency and pulmonary function, whereas risk assessment is based on exacerbation frequency and severity. These 2 measures determine the initial severity of asthma in the untreated patient as well as the degree of control in asthma once treatment has been initiated. The focus on asthma control is important because the attainment of control correlates with a better quality of life and reduction in health care use. We describe 4 easy steps to achieving asthma control in the ambulatory practice setting: (1) a standardized assessment of asthma symptoms using a 5-question assessment tool called the Asthma Control Test, (2) a simple mnemonic that provides a systematic review of the comorbidities and clinical variables that contribute to uncontrolled asthma, (3) directed patient education, and (4) a schedule for ongoing care. Most if not all patients can achieve good control of their asthma with optimal care through an active partnership with their health care professionals.

OBJECTIVE To evaluate our experience with patients who presented with chronic cough and how exhaled nitric oxide predicted response to inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS This retrospective observational study of 114 patients evaluated for chronic cough with measured exhaled nitric oxide and methacholine challenge testing was conducted from December 1, 2004, through November 30, 2005. Clinical records were extracted. Patients with no documented follow-up were contacted by telephone and administered a questionnaire. RESULTS In 64 patients, ICS therapy was started or the current ICS dose increased. Forty-one patients had elevated exhaled nitric oxide levels (defined as ≥35 ppb), 36 (88%) of whom had significant improvement in their chronic cough (likelihood ratio of a positive response, 4.9; 95% confidence interval, 2.2-10.9). Twenty-three patients with exhaled nitric oxide levels in the reference range were also prescribed ICS, and only 2 had cough improvement (likelihood ratio of a negative response, 0.07; 95% confidence interval, 0.02-0.25). Patients had documented follow-up that ranged from 4 weeks to 16 months. A cutoff of 38 ppb was found to best differentiate ICS responders and nonresponders. CONCLUSION Measurement of exhaled nitric oxide accurately predicted response to ICS therapy for chronic cough. Patients with a positive exhaled nitric oxide test result had a strong likelihood of response to ICS, whereas a negative exhaled nitric oxide test result indicated an unlikely response to ICS. This finding may potentially have an impact on how patients with chronic cough are evaluated and treated.

OBJECTIVE To identify the factors that patients consider most concerning about their cough. PATIENTS AND METHODS All consecutive patients who presented with a complaint of chronic cough between November 1, 2000, and February 28, 2001, were prospectively surveyed for cough-related complaints using an 18-item symptom-complaint questionnaire. We analyzed frequencies of responses and response patterns to specific items on the questionnaire. We also examined whether the responses to individual items related to the patient's age, sex, and duration of cough. RESULTS Of the 146 consecutive patients referred for evaluation of chronic cough, 136 were eligible for inclusion in the study. These patients cited feelings of frustration, irritability, or anger (43%), frequent physician visits and testing (41%), and sleep disturbances (38%) as the most prevalent major problems. The responses to individual items on the questionnaire were not related to patients' age, sex, and cough duration. Anxiety about underlying serious illness continued to be a concern for most patients. CONCLUSIONS Frustration, anger, or anxiety was the most frequent major problem cited by patients. Frequent physician visits and testing was the unexpected second most frequent major problem. These findings are important because most chronic cough guidelines are based on clinical efficacy and cost-effectiveness considerations rather than on patient satisfaction. Future studies regarding chronic cough evaluation should take into account patient satisfaction and perceived burden of disease as outcome variables.

Acute respiratory worsening (ARW) requiring hospitalization in patients with fibrotic interstitial lung disease (f-ILD) is common. Little is known about the frequency and implications of ARW in IPF and non-IPF ILD patients hospitalized for acute exacerbation (AE) vs known causes of ARW.All consecutive patients with f-ILD hospitalized with ARW at our institution from 2000 to 2014 were reviewed. ARW was defined as any worsening of respiratory symptoms with new or worsened hypoxemia or hypercapnia within 30 days of admission. Suspected AE was defined using modified 2007 American Thoracic Society/European Respiratory Society criteria. Known causes of ARW were reviewed and collated along with in-hospital and all-cause mortality postdischarge.A total of 220 patients (100 with IPF and 120 non-IPF) composed 311 admissions for ARW. Suspected AE (SAE) comprised 52% of ARW admissions, followed by infection (20%), and subacute progression of disease (15%). In-hospital mortality was similar in patients with IPF vs patients without (55 vs 45%, P = .18), but worse in suspected AE admission types (OR, 3.1 [1.9-5.14]). One-year survival after last ARW admission for the whole cohort was 22%, despite only 27% of patients presenting with baseline oxygen requirement at admission and a mean admission Charlson Comorbidity Index score of 5.4 (expected 1-year survival, 89%). Survival after discharge was similar between SAE and secondary ARW admission types in both IPF and non-IPF patients.Among patients with f-ILD, hospitalization for ARW appears associated with significant in-hospital and postdischarge mortality regardless of underlying fibrotic lung disease or non-AE cause of acute respiratory decline.

Background & aimsIt is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission.MethodsBetween April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score