Application of the ERS/ATS Spirometry Standards and Race-Neutral Equations in the COPDGene Study.

RATIONALE: The European Respiratory Society (ERS) and the American Thoracic Society (ATS) recommend using z-scores, and the ATS has recommended using Global Lung Initiative (GLI)- "Global" race-neutral reference equations for spirometry interpretation. However, these recommendations have been variably implemented and the impact has not been widely assessed, both in clinical and research settings. OBJECTIVES: We evaluated the ERS/ATS airflow obstruction severity classification. METHODS: In the COPDGene Study (n = 10,108), airflow obstruction has been defined as a forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio <0.70, with spirometry severity graded from class 1 to 4 based on race-specific percent predicted (pp) FEV1 cut-points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the GOLD approach, using NHANES III race-specific equations, to the application of GLI-Global equations using the ERS/ATS definition of airflow obstruction as FEV1/FVC ratio < lower limit of normal (LLN) and z-FEV1 cut-points of -1.645, -2.5, and -4 ("zGLI Global"). We tested the four-tier severity scheme for association with COPD outcomes. MEASUREMENTS AND MAIN RESULTS: The lowest agreement between ERS/ATS with zGLI Global and the GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD 1 and 2) and race was a major determinant of redistribution. After adjustment for relevant covariates, zGLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of COPD (Hazard Ratio 1.23, 95% CI 1.04-1.44, p=0.014), and showed a linear increase in exacerbation rates with increasing disease severity, in comparison to GOLD. CONCLUSIONS: The zGLI Global severity classification outperformed GOLD in the discrimination of survival, exacerbations, and imaging characteristics.

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease.

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomized to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (s.e.) of decline in forced vital capacity (FVC; ml/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (s.e.) change in FVC at week 52 was -86.4 (21.1) ml in the placebo group and -39.1 (22.2) ml in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (s.e.) change in FVC from baseline to week 52 of SENSCIS-ON was -41.5 (24.0) ml in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) ml in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT02597933 and NCT03313180.

Remotely supervised spirometry versus laboratory-based spirometry during the COVID-19 pandemic: a retrospective analysis.

BACKGROUND: The COVID-19 pandemic has constrained access to spirometry, and the inherent risk of infectious transmission during aerosol-generating procedures has necessitated the rapid development of Remotely Supervised Spirometry (RSS). This innovative approach enables patients to perform spirometry tests at home, using a mobile connected spirometer, all under the real-time supervision of a technician through an online audio or video call. METHODS: In this retrospective study, we examined the quality of RSS in comparison to conventional Laboratory-based Spirometry (LS), using the same device and technician. Our sample included 242 patients, with 129 undergoing RSS and 113 participating in LS. The RSS group comprised 51 females (39.5%) with a median age of 37 years (range: 13-76 years). The LS group included 63 females (55.8%) with a median age of 36 years (range: 12-80 years). RESULTS: When comparing the RSS group to the LS group, the percentage of accurate Forced Expiratory Volume in one second (FEV1) measurements was 78% (n = 101) vs. 86% (n = 97), p = 0.177; for Forced Vital Capacity (FVC) it was 77% (n = 99) vs. 82% (n = 93), p = 0.365; and for both FEV1 and FVC, it was 75% (n = 97) vs. 81% (n = 92), p = 0.312, respectively. CONCLUSIONS: Our findings demonstrate no significant difference in the quality of spirometry testing between RSS and LS, a result that held true across all age groups, including patients aged over 65 years. The principal advantages of remote spirometry include improved access to pulmonary function tests, reduced infectious risk to curtail disease spread, and enhanced convenience for patients.

Differences in percentage predicted spirometric values obtained with thirteen reference equations applied to healthy children.

BACKGROUND: There is limited information on the discrepancy between the spirometric values calculated with diverse spirometric prediction equations in normal children. OBJECTIVE: To determine the differences in percentage predicted (PP) values calculated through thirteen prediction equations (PEs) in healthy Chilean children. METHODS: We compared the PP values for FVC, FEV1, FEF25-75% and FEV1/FVC obtained by applying thirteen PEs, using GLI-2012 as a gold standard reference equation and including race neutral GLI-2022 in the analysis; PP values are from a group of 208 healthy Chilean children aged 7 to 17 years. RESULTS: In boys, the range of differences for FVC between PEs compared to the reference group went from -5.47% to 20.82% and from -6.4% to 19.74% in girls. For FEV1, in girls, the range of differences went from -5.96% to 18.01% and from -5,04% to 20.67% in boys. Significant differences between GLI-2012 PPs and the other PEs were observed more frequently in girls than in boys (p < 0.001). CONCLUSIONS: There is a wide difference between the spirometric PPs values by different PEs, including race neutral GLI-2022. Our findings, especially given the potential interpretative and clinical implications, might suggest the need for conducting standardized, multicenter studies in Latin America to determine which PEs would better fit pediatric populations in this region.

The initial angle of the maximum expiratory flow-volume curve: a novel start-of-test criteria of spirometry in children.

The aim of the present study was to define an initial angle called ß and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14 years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle ß was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle ß, and other spirometric parameters were compared among groups. The diagnostic values of angle ß, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle ß. The poor-quality group exhibited a significantly smaller angle ß (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle ß among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle ß and FET values indicated poor-quality MEFV curves. The combination of angle ß < 74.58° and FET < 4.91 s had a significantly larger area under the curve than either one alone. The normal value of angle ß of children aged 4-14 years was 78.40 ± 0.12°.   Conclusions: Angle ß contributes to the quality control evaluation of spirometry in children. Both angle ß < 74.58° and FET < 4.91 s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6 years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle ß, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle ß < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91 s offers a higher diagnostic value.

Predicting Exacerbations in Alpha-1 Antitrypsin Deficiency Using Clinical and Pulmonary Function Tests: Portuguese EARCO Registry.

INTRODUCTION: Exacerbations are common in individuals with alpha-1 antitrypsin deficiency (AATD)-related lung disease. This study intended to identify independent predictive factors for exacerbations in AATD using the Portuguese European Alpha-1 Research Collaboration (EARCO) registry. METHODS: This study includes patients from the Portuguese EARCO registry, a prospective multicenter cohort (NCT04180319). From October 2020 to April 2023, this registry enrolled 137 patients, 14 of whom were excluded for analysis for either missing 12 months of follow-up or baseline pulmonary function. RESULTS: Among the 123 AATD patients, 27 (22.0%) had at least one exacerbation in the last 12 months of follow-up. Patients with Pi*ZZ phenotype were three times more likely than the rest of the population to experience any exacerbation (32.7 vs. 14.1%, p = 0.014; OR 3.0). BODE index was significantly higher in exacerbators than in non-exacerbators (3.9 ± 2.4 vs. 1.3 ± 1.2; p < 0.001), including on multivariate analysis (p = 0.002). Similar results were found for BODEx (multivariate p < 0.001). DLCO was the only functional parameter independently associated with exacerbations (p = 0.024). CONCLUSIONS: DLCO, BODE, and BODEx were independent predictors of exacerbations at 12 months in AATD patients. Understanding these risk factors can aid decision-making on AATD-related lung disease management and improve patient outcomes.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease.

BACKGROUND: In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. METHODS: This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. RESULTS: FVC% (AUROC 0.77 [95%CI 0.72-0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70-0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58-0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93-0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94-0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values. CONCLUSIONS: Routinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Association of temperature and absolute humidity with incidence of exercise-induced bronchoconstriction in children.

AIM: Exercise test outdoors is widely used to diagnose asthma in children, but it is unclear how much outdoor air factors affect the results. METHODS: We analysed 321 outdoor exercise challenge tests with spirometry in children 6-16 years conducted due to suspicion of asthma or for assessing the effect of medication on asthma. We studied the association of FEV1 decrease and incidence of exercise-induced bronchoconstriction (EIB) with temperature, relative humidity (RH) and absolute humidity (AH). RESULTS: Asthma was diagnosed in 57% of the subjects. AH ≥5 g/m3, but not RH or temperature, was associated with the EIB incidence (p = 0.035). In multivariable logistic regression, AH ≥5 g/m3 was negatively associated (OR = 0.51, 95% CI [0.28─0.92], p = 0.026) while obstruction before exercise (OR = 2.11, 95% CI [1.16─3.86], p = 0.015) and IgE-mediated sensitisation were positively associated with EIB (OR = 2.24, 95% CI [1.11─4.51], p = 0.025). AH (r = -0.12, p = 0.028) and temperature (r = -0.13, p = 0.023) correlated with decrease in FEV1. In multivariable linear regression, only AH was associated with FEV1 decrease (coefficient = -0.044, 95% CI [-0.085 to -0.004], p = 0.033). CONCLUSION: AH of outdoor air associates with occurrence and severity of EIB in outdoor exercise tests in children. Care should be taken when interpreting negative outdoor exercise test results if AH of air is high.

COVID-19's Radiologic, Functional, and Serologic Consequences at 6-Month and 18-Month Follow-up: A Prospective Cohort Study.

BACKGROUND: We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities. METHODS: This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesionvolume), PFT, and IgG levels. RESULTS: This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesionvolume was significantly lower at 18 months than 6 months (P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months (P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesionvolume showed a positive correlation with IgG level (r = 0.643, P < 0.001). CONCLUSION: At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesionvolume and FVC improved between 6 and 18 months. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0008573.

Diagnostic utility of spirometry for children with induced laryngeal obstruction or chronic non-specific cough.

PURPOSE: To determine the diagnostic utility of spirometry in distinguishing children with Induced Laryngeal Obstruction (ILO) or chronic non-specific cough (a.k.a. tic cough) from those with mild or moderate to severe asthma. METHODS: Retrospective cross sectional design. Children diagnosed with ILO (N = 70), chronic non-specific cough (N = 70), mild asthma (N = 60), or moderate to severe asthma (N = 60) were identified from the electronic medical record of a large children's hospital. Spirometry was completed before ILO, non-specific cough, or asthma diagnoses were made by pediatric laryngologists or pulmonologists. Spirometry was performed following American Thoracic Society guidelines and was interpreted by a pediatric pulmonologist. Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), FEV1/FVC Ratio (FEV1/FVC), Forced Mid-Expiratory Flow 25--75 % (FEF25-75%), pulmonologist interpretation of flow volume loops, and overall exam findings were extracted from the medical record. RESULTS: Ninety seven percent of children with ILO or chronic non-specific cough presented with spirometry values within normative range. Patients with ILO, non-specific cough, and mild asthma presented with FVC, FEV1, FEV1/FVC, and FEF25-75% values in statistically similar range. Children with moderate to severe asthma presented with significantly reduced FVC (p < .001), FEV1 (p < .001), FEV1/FVC (p < .001), and FEF25-75% (p < .001) values when compared with patients in the other groups. Flow volume loops were predominantly normal for children with ILO and non-specific cough. CONCLUSIONS: Findings indicate that ILO and chronic non-specific cough can neither be diagnosed nor differentiated from mild asthma using spirometry alone. Spirometry should therefore be used judiciously with this population, bearing in mind the limitations of the procedure. Future research should determine the most effective and efficient ways of delineating ILO and non-specific cough from other respiratory conditions in children.

Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial.

BACKGROUND: There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma. OBJECTIVE: We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma. METHODS: We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/µL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV1 week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point. RESULTS: A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N = 22), 75 mg BID (N = 26), 150 mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P = .020) and the 75-mg BID (median, 0.17; P = .021) groups. Placebo-corrected FEV1 increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile. CONCLUSIONS: Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.

The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease.

BACKGROUND: Granulomatous and lymphocytic interstitial lung disease (gl-ILD) is a major cause of morbidity and mortality among patients with common variable immunodeficiency. Corticosteroids are recommended as first-line treatment for gl-ILD, but evidence for their efficacy is lacking. OBJECTIVES: This study analyzed the effect of high-dose corticosteroids (≥0.3 mg/kg prednisone equivalent) on gl-ILD, measured by high-resolution computed tomography (HRCT) scans, and pulmonary function test (PFT) results. METHODS: Patients who had received high-dose corticosteroids but no other immunosuppressive therapy at the time (n = 56) and who underwent repeated HRCT scanning or PFT (n = 39) during the retrospective and/or prospective phase of the Study of Interstitial Lung Disease in Primary Antibody Deficiency (STILPAD) were included in the analysis. Patients without any immunosuppressive treatment were selected as controls (n = 23). HRCT scans were blinded, randomized, and scored using the Hartman score. Differences between the baseline and follow-up HRCT scans and PFT were analyzed. RESULTS: Treatment with high-dose corticosteroids significantly improved HRCT scores and forced vital capacity. Carbon monoxide diffusion capacity significantly improved in both groups. Of 18 patients, for whom extended follow-up data was available, 13 achieved a long-term, maintenance therapy independent remission. All patients with relapse were retreated with corticosteroids, but only one-fifth of them responded. Two opportunistic infections were found in the corticosteroid treatment group, while overall infection rate was similar between cohorts. CONCLUSIONS: Induction therapy with high-dose corticosteroids improved HRCT scans and PFT results of patients with gl-ILD and achieved long-term remission in 42% of patients. It was not associated with major side effects. Low-dose maintenance therapy provided no benefit and efficacy was poor in relapsing disease.

Mortality and Associated Factors in Patients with Systemic Sclerosis Associated Pulmonary Hypertension with and without Interstitial Lung Disease: A Long-Term Follow-up Study.

OBJECTIVES: We aimed to analyze the prevalence, mortality, and prognostic factors in systemic sclerosis (SSc) patients with pulmonary hypertension (PH) with or without interstitial lung disease (ILD). METHODS: The associations between mortality and demographics, transthoracic echocardiography, right heart catheterization (RHC), pulmonary functional parameters at baseline, and treatment modalities in two groups; patients with pulmonary arterial hypertension (PAH, PH without significant ILD) and PH + ILD were evaluated. RESULTS: The mean age of the patients was 56.6±13.5 (range: 34-82, 44 women/ 2 men), and 23 (52.3%) were deceased during a median follow-up of 45 months. The survival rates of PH-SSc patients were 91% for the first year, 75% for 2 years, 68% for 3 years, and 43.1% for 5 years. The majority of deceased patients were in the PH + ILD group (p=0.007). The PH + ILD group had more diffuse skin involvement, anti-Scl-70 positivity, high C-reactive protein, low FVC, and lower DLCO values. The deceased patients had higher ePASP, low CO, and FVC values compared to surviving patients. Median survival time was significantly better in patients on combined therapy (44 vs. 61 months, p=0.01). The mortality-related factors in the PH + ILD group were decreased initial FVC, high ePASP on echocardiography, low cardiac output on RHC, deteriorated functional class, and monotherapy. CONCLUSION: This is the first reported SSc-PH cohort from Turkey by a multidisciplinary team after the implementation of PAH-specific drugs. SSc-PH is a severe complication of SSc with high mortality especially in patients with accompanying severe ILD.

Prediction model for respiratory-related mortality in microscopic polyangiitis with interstitial lung disease: multicenter REVEAL cohort study.

OBJECTIVE: This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. METHODS: We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments, and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution computed tomography (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. RESULTS: Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar hemorrhage (DAH), and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLco), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLco, and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLco, and presence of honeycombing on chest HRCT (MPF model). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. CONCLUSIONS: Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD.

Association Between Pretreatment Chest Imaging and Immune Checkpoint Inhibitor Pneumonitis Among Patients With Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. METHODS: We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. RESULTS: A total of 471 patients with lung cancer were included, of which 402 had non-small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69-16.92; P<.001; and HR, 2.81; 95% CI, 1.50-5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17-18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3-5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. CONCLUSIONS: Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.

Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.

OBJECTIVES: To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort. METHODS: A total of 25 subjects were involved in this study including COPD (n = 8), MCTE (n = 3), and healthy (n = 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins. RESULTS: The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p = 0.02) and (ii) dependent on the age of the subjects in the healthy group (p = 0.0008) while their CVs (p = 0.13) were not. CONCLUSION: The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group. KEY POINTS: • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort.

Skin disorders and interstitial lung disease: Part I-Screening, diagnosis, and therapeutic principles.

Numerous inflammatory, neoplastic, and genetic skin disorders are associated with interstitial lung disease (ILD), the fibrosing inflammation of lung parenchyma that has significant morbidity and mortality. Therefore, the dermatologist plays a major role in the early detection and appropriate referral of patients at risk for ILD. Part 1 of this 2-part CME outlines the pathophysiology of ILD and focuses on clinical screening and therapeutic principles applicable to dermatological patients who are at risk for ILD. Patients with clinical symptoms of ILD should be screened with pulmonary function tests and high-resolution chest computed tomography. Screening for pulmonary hypertension should be considered in high-risk patients. Early identification and elimination of pulmonary risk factors, including smoking and gastroesophageal reflux disease, are essential in improving respiratory outcomes. First-line treatment interventions for ILD in a dermatological setting include mycophenolate mofetil, but the choice of therapeutic agents depends on the nature of the primary disease, the severity of ILD, and comorbidities and should be the result of a multidisciplinary assessment. Better awareness of ILD among medical dermatologists and close interdisciplinary collaborations are likely to prevent treatment delays improving long-term outcomes.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Beyond forced exhalation: impulse oscillometry as a promising tool for bronchial hyperresponsiveness evaluation.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.