The impact of lung transplantation on esophageal motility and inter-relationships with reflux and lung mechanics in patients with restrictive and obstructive respiratory disease.

BACKGROUND: For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed. METHODS: We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx. KEY RESULTS: RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05). CONCLUSIONS AND INFERENCES: RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

Risk of 30-Day All-Cause Readmission in Interstitial Lung Disease Patients after COVID-19: National-Level Data.

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

Impact of concomitant gastroesophageal reflux disease symptomology on prognosis and pulmonary function of chronic hypersensitivity pneumonitis.

Background and Objectives: Comorbid risk factors in chronic hypersensitivity pneumonitis (CHP) are poorly characterised. Gastroesophageal reflux disease (GERD) is linked to interstitial lung diseases like idiopathic pulmonary fibrosis (IPF), but its association and treatment in CHP is less understood. This study aims to understand the role and prevalence of GERD in CHP, plus the effect of GERD treatment on lung function and mortality. Methods: A tertiary referral centre panel was retrospectively reviewed for 214 patients diagnosed with CHP based on clinical history, bronchoalveolar lavage fluid analysis, imaging and histopathology. GERD diagnostic criteria included symptomology, acid suppressive therapy use and diagnostic testing. CHP patients with GERD (n = 89) and without GERD (n = 125) were compared via descriptive statistical analysis. Pulmonary function, GERD diagnosis plus treatment and other comorbidities were evaluated against CHP outcomes. Results: Respective differences between diagnosis and study termination dates in the GERD population versus without GERD for functional vital capacity (FVC) were - 1 L vs - 2.5 L, diffusing capacity of the lungs for carbon monoxide (DLCO) were - 2 mL/min/mmHg versus - 1 mL/min/mmHg, per cent alive at the time of study 88% versus 81%, median date of survival 574.5 versus 850 and supplemental oxygen requirement 41% versus 37%. GERD prevalence was higher in CHP patients relative to the general population. No statistical significance was found between survival curves, oxygen requirement, smoking history, FVC, or DLCO. Conclusions: GERD could be a harmful comorbidity in CHP though may not necessarily affect survival or functional outcomes. This aligns with previous IPF studies, though remains controversial. Further research is needed regarding this association and treatment benefit.

The Role of Radiology in Multidisciplinary Discussion of Patients With Interstitial Lung Diseases.

Radiologists fulfill a vital role in the multidisciplinary care provided to patients with interstitial lung diseases and other diffuse parenchymal lung disorders. The diagnosis of interstitial lung diseases hinges on the consensus of clinical, radiology, and pathology medical subspecialists, but additional expertise from rheumatology, immunology, or hematology can be invaluable. The thin-section computed tomography (CT) features of lung involvement informs the diagnostic approach. Radiologists should be familiar with radiologic methods (including inspiratory/expiratory and prone imaging) and be well versed in the recognition of the CT features of fibrosis, assessment of the overall pattern of lung involvement, and classification according to the latest guidelines. We present a case-based review that highlights examples wherein CT features and subspecialist radiologist interpretation informed the multidisciplinary team consensus diagnosis and care pathways.

Derivation and validation of a prediction model for histopathologic fibrotic hypersensitivity pneumonitis.

BACKGROUND: Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD). OBJECTIVE: We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved. METHODS: Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables. Using elastic net logistic regression, a penalized regression approach to minimize overfitting, a clinical model built on non-invasive assessments was derived for the prediction of histopathologic f-HP. This model was then validated in an independently derived external cohort from three sites. RESULTS: The derivation and validation cohorts consisted of 248 (84 cHP and 164 other f-ILD) and 157 (82 f-HP and 75 other f-ILD) histopathologically-defined patients, respectively (total study N = 405). Variables retained from the elastic net model included age in years (regression coefficient 0.033), male sex (-1.109), positive exposure history (1.318), percent predicted forced vital capacity (-0.021), radiologic peribronchovascular axial ILD distribution (0.199), mid (-0.22) or lower lobe (-0.839) craniocaudal or patchy (0.287) ILD distribution, upper (1.188) or equivalent upper and lower lobe (0.237) traction bronchiectasis, mosaic attenuation (1.164), and centrilobular nodules (2.045). Bias corrected AUC was 0.84 (standard error = 0.02) for the derivation cohort and 0.80 (CI 0.73-0.87) for the validation cohort. CONCLUSIONS: This multivariable model demonstrated good predictive performance for delineating histopathologically-defined f-HP from other f-ILD as a means of avoiding or justifying biopsy and supporting MDD diagnostic confidence.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

The Perils and Pitfalls of Esophageal Dysmotility in Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF. METHODS: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment. RESULTS: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008). DISCUSSION: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs.

Particulate generation with different oxygen delivery devices.

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.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Characterizing Particulate Generation During Cardiopulmonary Rehabilitation Classes With Patients Wearing Procedural Masks.

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.

Interstitial Lung Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients: Comparison With Idiopathic Pulmonary Fibrosis.

BACKGROUND/OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may involve the kidney, respiratory tract, skin, or central and peripheral nervous system. Reports of interstitial lung disease (ILD) in AAV (AAV-ILD) have been increasing. METHODS: We reviewed the medical records of all patients with AAV-ILD between January 1, 2007, and December 31, 2017, and compared their pulmonary involvement to patients with idiopathic pulmonary fibrosis (IPF). RESULTS: We identified 24 patients with AAV-ILD: 14 with microscopic polyangiitis, 8 with granulomatosis with polyangiitis, and 2 with eosinophilic granulomatosis with polyangiitis. Perinuclear or myeloperoxidase ANCA was present in 16 cases (66.7%), whereas cytoplasmic or proteinase 3 ANCA was positive in 8 (33.3%). Usual interstitial pneumonia (UIP) was seen in 11 (45.8%), probable UIP in 1 (4.2%), indeterminate UIP in 2 (8.3%), and an alternate diagnosis in 10 (41.7%), and was further characterized as chronic hypersensitivity pneumonitis-like pattern seen in 6 (25%), nonspecific interstitial pneumonia-like pattern in 3 (12.5%), and cryptogenic organizing pneumonia-like pattern in 1 (4.2%). Forced vital capacity and diffusing capacity declined over time in patients with AAV-ILD. When compared with the IPF cohort, patients with AAV-ILD had intermediate survival and speed of lung function decline (3-year survival in AAV-ILD group was 94% vs 69% in IPF). CONCLUSIONS: Antineutrophil cytoplasmic antibody-associated vasculitis ILD is a progressive and potentially fatal condition. Although most cases in the literature are associated with p-ANCA and positive myeloperoxidase, we found that a third of patients had c-ANCA or granulomatosis with polyangiitis. Our cohort adds experience in this rare manifestation of AAV.

Consensus Guidelines for Evaluation and Management of Pulmonary Disease in Sjögren's.

BACKGROUND: Pulmonary disease is a potentially serious yet underdiagnosed complication of Sjögren's syndrome, the second most common autoimmune rheumatic disease. Approximately 16% of patients with Sjögren's demonstrate pulmonary involvement with higher mortality and lower quality of life. RESEARCH QUESTION: Clinical practice guidelines for pulmonary manifestations of Sjögren's were developed by the Sjögren's Foundation after identifying a critical need for early diagnosis and improved quality and consistency of care. STUDY DESIGN AND METHODS: A rigorous and transparent methodology was followed according to American College of Rheumatology guidelines. The Pulmonary Topic Review Group (TRG) developed clinical questions in the PICO (Patient, Intervention, Comparison, Outcome) format and selected literature search parameters. Each article was reviewed by a minimum of two TRG members for eligibility and assessment of quality of evidence and strength of recommendation. Guidelines were then drafted based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale and data extraction tables were submitted to a Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: The literature search revealed 1,192 articles, of which 150 qualified for consideration in guideline development. Of the original 85 PICO questions posed by the TRG, 52 recommendations were generated. These were then reviewed by the Consensus Expert Panel and 52 recommendations were finalized, with a mean agreement of 97.71% (range, 79%-100%). The recommendations span topics of evaluating Sjögren's patients for pulmonary manifestations and assessing, managing, and treating upper and lower airway disease, interstitial lung disease, and lymphoproliferative disease. INTERPRETATION: Clinical practice guidelines for pulmonary manifestations in Sjögren's will improve early identification, evaluation, and uniformity of care by primary care physicians, rheumatologists, and pulmonologists. Additionally, opportunities for future research are identified.

Reflux-Aspiration in Chronic Lung Disease.

Microaspiration, or silent aspiration, is commonly suspected in patients with refractory respiratory symptoms, including unexplained chronic cough, asthma, chronic obstructive pulmonary disease, bronchiolitis, bronchiectasis, and idiopathic pulmonary fibrosis. This suspicion is driven by the high prevalence of gastroesophageal reflux in these otherwise disparate disorders. Frequently, patients receive aggressive treatment for gastroesophageal reflux disease as a means of treating their underlying respiratory conditions, even in the absence of overt symptoms of reflux. However, clinical trials have not demonstrated a clear impact on outcomes with this strategy, and in some instances there may be potential for harm. Mechanistic studies have increasingly used gastric biomarkers obtained directly from the airways to confirm the association between reflux and respiratory disease, but results are limited by methodologic flaws and correlation. The best evidence of aspiration directly causing respiratory disorders is the histopathologic detection of foreign bodies. For most of the other chronic respiratory disorders, microaspiration may be uncommon or a secondary aggravating factor, as in patients with acute exacerbations of chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. In some cases, microaspiration is probably not a significant factor at all, such as in unexplained chronic cough. It is important to distinguish between conditions in which aspiration is primarily or directly causal and conditions in which aspiration may be indirectly aggravating, to help identify whether interventions targeting reflux and aspiration precautions should be recommended to patients. Our clinical review examines some of the evidence supporting reflux-aspiration as a mechanism for several chronic respiratory disorders and offers some management considerations when reflux-aspiration is suspected.