Percent-predicted Forced Vital Capacity Research Articles

Lung imaging patterns in connective tissue disease–associated interstitial lung disease impact prognosis and immunosuppression response

Abstract Objectives Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response. Methods Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. Results Among 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP. Conclusion Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Antioxidant diet/lifestyle could mitigate the adverse impacts of urinary polycyclic aromatic hydrocarbons on lung function

BackgroundExtant research has demonstrated a correlation between exposure to polycyclic aromatic hydrocarbons (PAHs) and impaired lung function. The maintenance of an antioxidant-rich diet/lifestyle positively benefits pulmonary health. However, the potential ameliorative impact of an antioxidant-based diet/lifestyle on PAH-induced detrimental effects remains unclear. MethodsThe study drew upon cross-sectional data encompassing 1615 participants derived from the National Health and Nutrition Examination Survey 2007 to 2012. To gauge the maintenance of an antioxidant-rich diet/lifestyle, we employed Oxidative Balance Score (OBS) that incorporates sixteen nutrients and four lifestyle factors. Lung function was evaluated using percent-predicted Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1), FEV1/FVC, and fractional exhaled nitric oxide (FENO). Our analytical approach entailed the utilization of weighted linear models. ResultsOur analysis unveiled interaction effects between urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and OBS concerning lung function. A one-unit increase in ∑OH-PAH (sum of eight OH-PAHs) was linked to a −0.75% reduction (95% CI: −1.28, −0.22) in FEV1/FVC. Individuals exhibiting low OBS displayed a marked decrease in FEV1/FVC (mean difference = −1.10%; 95% CI: −1.82, −0.39) for each unit increase in ∑OH-PAH, whereas no significant associations were discerned for those with medium or high OBS. Further stratification by gender yielded consistent results. The correlation between ∑OH-PAH and FENO proved statistically significant among participants with low OBS (P = 0.002) and medium OBS (P = 0.001), but non-significant for those with high OBS. Parallel findings emerged when examining percent-predicted FEV1 and FVC. ConclusionsIn conclusion, our study underscores the existence of statistically significant interactions between OH-PAHs and the maintenance of an antioxidant-rich diet and lifestyle concerning lung function. These findings underscore the pivotal role of maintaining an antioxidant-based diet and lifestyle in mitigating the adverse impacts of PAH exposure on lung function.

Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis.

Background: Preliminary evidence for efficacy in pulmonary sarcoidosis has been shown for efzofitimod. Here we present supportive evidence of efficacy based on an exposure-response analysis. Methods: Data from two studies (Phase 1, N = 24, single dose in healthy volunteers, and Phase 1b/2a, N = 25, multiple doses over 24weeks in participants with pulmonary sarcoidosis) were used to build a population pharmacokinetic model. Using this model, the relationship between efzofitimod exposure and three prespecified efficacy parameters [mean daily oral corticosteroid (OCS) dose, percent-predicted forced vital capacity (ppFVC) and King's Sarcoidosis Questionnaire-Lung (KSQ-Lung) score] was explored. Linear regression described the relationship of efzofitimod exposure and OCS reduction, ppFVC and KSQ-Lung score. Logistic regression related efzofitimod exposure to the probability of achieving a minimal clinically important difference for ppFVC and KSQ-Lung score. Due to the small study size, trends (not statistical significance) in relationships are reported. Results: In patients with pulmonary sarcoidosis, as efzofitimod exposure increased, the mean daily OCS dose decreased, and ppFVC and KSQ-Lung score improved over baseline. The slope for all the endpoints by both linear and logistic regression showed an improving trend with increased exposure. Conclusion: These preliminary findings of a positive exposure-response across multiple efficacy endpoints support the claim that proof of concept has been established for the use of efzofitimod in pulmonary sarcoidosis. Clinical Trial Registration: clinicaltrials.gov, identifier NCT03824392.

Predicting New-onset Exertional and Resting Hypoxemia in Fibrotic Interstitial Lung Disease.

Rationale: Hypoxemia in fibrotic interstitial lung disease (ILD) indicates disease progression and is of prognostic significance. The onset of hypoxemia signifies disease progression and predicts mortality in fibrotic ILD. Accurately predicting new-onset exertional and resting hypoxemia prompts appropriate patient discussion and timely consideration of home oxygen. Objectives: We derived and externally validated a risk prediction tool for both new-onset exertional and new-onset resting hypoxemia. Methods: This study used ILD registries from Canada for the derivation cohort and from Australia and the United States for the validation cohort. New-onset exertional and resting hypoxemia were defined as nadir oxyhemoglobin saturation < 88% during 6-minute-walk tests, resting oxyhemoglobin saturation < 88%, or the initiation of ambulatory or continuous oxygen. Candidate predictors included patient demographics, ILD subtypes, and pulmonary function. Time-varying Cox regression was used to identify the top-performing prediction model according to Akaike information criterion and clinical usability. Model performance was assessed using Harrell's C-index and goodness-of-fit (GoF) likelihood ratio test. A categorized risk prediction tool was developed. Results: The best-performing prediction model for both new-onset exertional and new-onset resting hypoxemia included age, body mass index, a diagnosis of idiopathic pulmonary fibrosis, and percent predicted forced vital capacity and diffusing capacity of carbon monoxide. The risk prediction tool exhibited good performance for exertional hypoxemia (C-index, 0.70; GoF, P = 0.85) and resting hypoxemia (C-index, 0.77; GoF, P = 0.27) in the derivation cohort, with similar performance in the validation cohort except calibration for resting hypoxemia (GoF, P = 0.001). Conclusions: This clinically applicable risk prediction tool predicted new-onset exertional and resting hypoxemia at 6 months in the derivation cohort and a diverse validation cohort. Suboptimal GoF in the validation cohort likely reflected overestimation of hypoxemia risk and indicated that the model is not flawed because of underestimation of hypoxemia.

Association of oxidative balance score and lung health from the National Health and Nutrition Examination Survey 2007-2012.

Oxidative stress is associated with outcomes of chronic lung disease. The oxidative stress-related exposures of diet and lifestyle can be evaluated by the oxidative balance score (OBS), and higher OBS scores indicate more significant antioxidant exposures. But the relationship between OBS and lung health is unknown. The aim of this study was to explore the association between OBS and lung health (respiratory symptoms, chronic lung disease, and lung function). A series of models, including weighted linear models, weighted logistic regression, and weighted multinomial logistic regression, were performed to assess the associations of OBS with respiratory symptoms, chronic lung disease, and lung function. The models adjusted by age, race/ethnicity, gender, educational background, poverty-to-income ratio, and dietary energy were also performed. Cross-sectional data of 5,214 participants from the National Health and Nutrition Examination Survey for the years 2007-2012 were analyzed. For every one-unit increase in OBS, the odds of wheezing/chronic bronchitis decreased by 6%. Increased OBS was associated with higher percent-predicted forced expiratory volume in one second (FEV1) (adjusted mean difference (MD), 0.21%; 95% CI: 0.10-0.32) and percent-predicted forced vital capacity (FVC) (adjusted MD, 0.15%; 95% CI: 0.07-0.24). A significantly lower risk of wheezing/chronic bronchitis was found in participants in the second/third/fourth OBS quartile compared to those in the first OBS quartile (all P for trend < 0.05). Moreover, higher percent-predicted FEV1 and FVC were also found in the third quartile and fourth quartile (all P for trend < 0.05). Furthermore, both dietary and lifestyle components were tightly related to pulmonary outcomes. Many associations were maintained after stratified by sex or after sensitivity analyses. Oxidative balance score was negatively correlated with the diagnosis of chronic bronchitis/wheezing/restrictive spirometry pattern and positively correlated with percent-predicted FVC and FEV1. It seems that the higher the OBS score, the better the pulmonary outcomes. The findings highlight the importance of adherence to an antioxidant diet and lifestyle and that it contributes to lung health.

P.65 Consistency of changes in percent-predicted forced vital capacity between real-world data and trial placebo arms in ambulatory Duchenne muscular dystrophy

Use of real-world and natural history data (RWD/NHD) as external controls for pulmonary outcomes is of interest for drug development in ambulatory Duchenne muscular dystrophy (DMD). However, differences across patient populations and RWD/NHD settings raise appropriate concerns about risk of bias. To assess this risk, we compared change in pulmonary function, as measured by percent-predicted forced vital capacity (FVC%p) between RWD/NHD sources and trial placebo arms in ambulatory boys with DMD. RWD/NHD data came from PRO-DMD-01, UZ Leuven, the North Star UK Clinical Network and Cincinnati Children's Hospital Medical Center. Placebo arm data came from phase 3 trials of tadalafil and drisapersen, and one phase 2 trial of drisapersen. PRO-DMD-01 and drisapersen trial data were provided by CureDuchenne. Change in FVC%p over 48-week intervals was studied in ambulatory, steroid-treated boys aged ≥5 years with baseline FVC%p > 50%. Primary analyses included 409 48-week intervals (263 patients) from RWD/NHD, and 161 intervals (161 patients) from placebo arms. At baseline, average ages in these groups were 9.5 and 8.8 years, respectively, and averages for FVC%p were 97.2% and 103.6%. Mean 48-week change in FVC%p was 2.9% greater in in RWD/NHD vs. placebo arms (95% confidence interval [CI]: -1.0%, 6.7%; p=0.14) in unadjusted analyses. After adjusting for baseline status (age, FVC%p, steroid type, height, weight, body mass index, North Star Ambulatory Assessment total score, and 10-meter walk run and rise from supine velocities) the difference in FVC%p between RWD/NHD and placebo arms decreased to -0.1% (95% CI: -3.6, 3.5; p=0.97). Similarly high consistency was observed in sensitivity analyses adjusting for fewer baseline characteristics. These findings are encouraging for use of external controls for FVC%p outcomes in this population. Additional research is needed to assess consistency of FVC%p over longer-time frames, and among older and non-ambulatory boys.

Pulmonary function after thoracoplasty for adolescent idiopathic scoliosis: a systematic review and meta-analysis.

Thoracoplasty is a procedure which involves rib resection from the costovertebral junction to the apex of the rib hump deformity to address the cosmetic concerns of patients of scoliosis. There is conflicting literature on its effect on pulmonary function. The present meta-analysis was conducted to review and analyze the available literature and ascertain the effect of thoracoplasty on pulmonary function. Search was conducted according to PRISMA guidelines on three databases. After analysis of all the search results by title, abstracts and full texts-10 studies were identified for inclusion in the review. We included studies which had analyzed preoperative and postoperative pulmonary function tests (PFTs) after thoracoplasty. Pooled estimates were calculated for pulmonary function, and effect of other factors was analyzed by subgroup analysis and meta-regression. The included studies were published between 1998 and 2019. A total of 385 patients were included in these studies, with a mean age of 15.01years, with a female preponderance. Apprehension over appearance of rib hump was the most common indication for thoracoplasty. Percent-predicted forced vital capacity(FVC) and forced expiratory volume in 1s (FEV-1) were significantly decreased on follow-up. Anterior approach to corrective surgery and lower age were found to be associated with worse pulmonary function. Preoperative Cobb's angle was found to have significant impact on decrease in FEV-1 only, but not on other PFT parameters. Overall decrease in pulmonary function after thoracoplasty necessitates the need of adequate preoperative pulmonary function to mitigate its effect on patient well-being. Use of a posterior approach for corrective surgery when thoracoplasty is planned might lead to better outcomes. More research is needed to study effect of preoperative Cobb's angle on pulmonary function.

Comparison of Slow and Forced Vital Capacity on Ability to Evaluate Respiratory Function in Bulbar-Involved Amyotrophic Lateral Sclerosis.

Background and ObjectiveThe percent-predicted forced vital capacity (FVC%) in the pulmonary function test (PFT) is generally used to evaluate the respiratory function in amyotrophic lateral sclerosis (ALS). The slow vital capacity (SVC) is another method to evaluate the respiratory function. Some neurologists found that the FVC% was not reflective of respiratory symptoms and the percent-predicted SVC (SVC%) was found to be higher in some patients with bulbar-onset ALS. We aimed to compare the percent predicted SVC (SVC%) with FVC% in evaluating the respiratory function and investigate the associations between the associations between clinical characteristics and the difference between the SVC% and the FVC% (SVC%-FVC%) in bulbar-involved ALS patients.MethodThis prospective study included patients with bulbar-involved ALS who visited the Peking University Third Hospital between October 2020 and November 2021. They underwent comprehensive clinical assessments, including bulbar symptom assessments, revised ALS functional rating scale (ALSFRS-R), Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (Roads), and PFTs. The group differences were analyzed using parametric and non-parametric tests.ResultsA total of 59 participants were initially enrolled, and 51 of them were included in the final analysis. In patients with bulbar-involved ALS, the SVC% (73.82 ± 21.95%) was significantly higher (p = 0.013) than the FVC% (71.42 ± 23.15%). After controlling for other relevant variables, a partial correlation analysis showed a significant correlation (r = −0.352, p = 0.041) between ALSFRS-R1 score and SVC%-FVC%.ConclusionOur prospective study found that the SVC% was significantly higher and more reflective of actual respiratory function than the FVC% in patients with bulbar-involved ALS. Furthermore, the severity of dysarthria was found to be positively correlated with SVC%-FVC%, providing a clinical marker for predicting SVC%-FVC%.

Human epididymis protein 4 is associated with severity and poor prognosis of connective tissue disease-associated interstitial lung disease with usual interstitial pneumonia pattern

BackgroundOverexpression of human epididymis protein 4 (HE4) was previously described in idiopathic pulmonary fibrosis (IPF), but whether serum HE4 can be considered as a potential biomarker in connective tissue disease-associated interstitial lung disease (CTD-ILD) with usual interstitial pneumonia (UIP) pattern was still unknown. MethodA total of 55 CTD-ILD patients with UIP pattern (UIP-CTD) and 52 healthy controls were enrolled in this study. The serum levels of HE4 and Krebs von den Lungen-6 (KL-6) were evaluated in both cohorts. In addition, immunohistochemistry analysis for HE4 was performed on the lung sections of 6 patients with rheumatoid arthritis-associated UIP (UIP-RA) and 6 patients with early-stage lung cancer as normal control. ResultsThe levels of serum HE4 and KL-6 were higher in patients with UIP-CTD than in healthy controls (292.3 pmol/L versus 79.5 pmol/L for HE4, p < 0.001; 1091.0 IU/mL versus 171.5 IU/mL for KL-6, p < 0.001). Significant correlations between serum HE4 levels and percentpredicted forced vital capacity (FVC%) (r = -0.425, p = 0.004), percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r = -0.447, p = 0.003), and Gender-Age-Physiology (GAP) index (r = 0.494, p < 0.001) were observed in UIP-CTD patients. In immunohistochemistry analysis, elevated expression of HE4 in bronchiolar epithelium and mesenchyme was observed in patients with UIP-RA compared with controls. The serum levels of HE4 (≥277.5 pmol/L) and GAP index were related to an increased risk of mortality (HR = 3.884, p = 0.034; HR = 1.480, p = 0.028, respectively). ConclusionThe expression of HE4 in serum and lung specimens was significantly elevated in UIP-CTD patients. Moreover, serum HE4 may be utilized as a biomarker to evaluate the severity of disease and predict the prognosis of UIP-CTD patients.

Chemotherapy for patients with advanced lung cancer with interstitial lung disease: a prospective observational study.

Introduction:Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important.Methods:Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy.Results:Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66–95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4–29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00–1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31–53)/8.9 months (95% CI: 7.6–11.8) and 91% (95% CI: 76–98)/12.2 months (95% CI: 9.2–14.5), respectively.Conclusion:AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

Is There a Correlation Between Cobb Angle and Pulmonary Function Tests at 2-year Follow-up in Patients With Severe Spinal Deformity Treated by Posterior Vertebral Column Resection?

Study design:A retrospective study.Objective:The aim was to evaluate the relationships of Cobb angle and pulmonary function tests (PFTs) changes in severe spinal deformity and underwent posterior vertebral column resection (PVCR).Summary of Background Data:No previous study focused on the correlation of deformity correction and PFTs changes in patients with cobb angle >90 degrees.Methods:PFTs values [forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and percent-predicted values FVC%, FEV1%] were evaluated preoperative and at 2 years after PVCR. FVC% <80% were defined as restrictive ventilation dysfunction (RVD), the severity of RVD were divided into mild (FEV1% ≥70%), moderate (70% > FEV1% ≥50%) and severe (FEV1% <50%). The relationships among PFTs values improvements and all possible impact factors (mainly correction cobb angle) collected in this study were analyzed. PFTs data were compared among the 3 RVD subgroups (mild vs. moderate vs. severe) and between residual >30 versus <30 degrees.Results:A total of 53 cases (28 male/25 female, mean ages 18.9 Y) underwent PVCR in one center from 2004 to 2016 were enrolled cobb angle. When 2 years after PVCR, average PFTs values showed significant improvements. PFTs values changes showed no correlation with correction rate and correction angle. The only significant impact factor in this study for FVC, FVC%, FEV1 improvements was preoperative FVC% and the only impact factor for FEV1% improvement was preoperative FEV1%, the relationships were negative. In accordance with the regression analysis, PFTs values improvements among the 3 RVD subgroups from high to low was severe>moderate>mild. However, patients with residual cobb angle <30 degrees had less PFTs values improvements than patients with residual cobb angle >30 degrees.Conclusions:Two years after PVCR, PFTs values were significantly improved. There is no linear correlation between cobb angle change and PFTs values improvements. Lower preoperative FVC% and FEV1% indicate more PFTs values improvements at 2 years post-PVCR.Level of Evidence:Level III.

Long-term evaluation of pulmonary function and survival of patients with interstitial pneumonia with autoimmunefeatures.

Interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease with autoimmune features who do not meet criteria for a connective tissue disease (CTD). Previous studies showed a wide variation in the radiologic pattern, pulmonary function and prognosis but there is still limited data on longitudinal outcomes. We aim to describe the long-term pulmonary function, radiological patterns, and survival of IPAF patients and explore a classification based on CTD-like subgroups by using clinical/serologic data. Retrospective analysis of IPAF patients who were sub-classified into six CTD-(like) subgroups: systemic lupus erythematosus-like, rheumatoid arthritis-like, Sjögren's syndrome-like, scleroderma, myositis-like, and unclassifiable. Linear mixed-effect models were used to compare the change in percent-predicted forced vital capacity (FVC%), percent-predicted diffusion capacity (DLCO%), and six-minute walk distance (SMWD) over time; and survival in the entire cohort and according to CTD-like subgroups and radiological patterns. Fifty-nine patients fulfilled IPAF criteria. FVC%, DLCO%, and SMWD remained stable over time. There was no difference between usual interstitial pneumonia (UIP) versus non-UIP radiologic patterns. Thirty-five patients were sub-classified into CTD-like subgroups. Survival decreased from 79% at 60 months to 53% at 120 months in the entire cohort but was similar among CTD-like subgroups and radiological patterns. Long-term pulmonary function and six-minute walk test remained stable over 36 months in our IPAF cohort. Prognosis and pulmonary function in UIP had similar outcomes compared to non-UIP. Although 40% of IPAF patients could not be sub-classified, our exploratory subclassification stratified 60% of patients into a CTD-like subgroup.

Percentage of residual B cells after 2weeks of rituximab treatment predicts the improvement of systemic sclerosis-associated interstitial lung disease.

The benefit of rituximab (RTX) for systemic sclerosis-associated interstitial lung disease (SSc-ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B-cell responsiveness to RTX is related to therapeutic effect. Ten SSc-ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B-cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24weeks after the first RTX administration, along with percent-predicted forced vital capacity (%FVC) before and 24weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2weeks after RTX was negatively correlated with the %FVC improvement at the 24-week assessment (r=-0.41, p=0.04). In the subgroup with less than 5% B-cell persistence at week 2, %FVC at the 24-week assessment was significantly improved compared to baseline (p=0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24weeks compared to baseline (p=0.41). In conclusion, the removal rate of B cells after 2weeks of RTX treatment may be a useful surrogate marker of subsequent SSc-ILD improvement.

Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences?

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC

IntroductionCheckpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti–programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development. MethodsPatients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP−: did not develop CIP) was determined clinically. Generalized estimating equation–based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC. ResultsA total of 43 patients (34 CIP−, 9 CIP+) with 79 PFTs (59 CIP−, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP− group (95% confidence interval: −38.6 to −4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP− cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively. ConclusionsPretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

Effects of obesity on pulmonary function considering the transition from obstructive to restrictive pattern from childhood to young adulthood.

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Validation and minimum important difference of the UCSD Shortness of Breath Questionnaire in fibrotic interstitial lung disease

RationaleThe University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) is a frequently used domain-specific dyspnea questionnaire; however, there is little information available regarding its use and minimum important difference (MID) in fibrotic interstitial lung disease (ILD). We aimed to describe the key performance characteristics of the UCSDSOBQ in this population.MethodsUCSDSOBQ scores and selected anchors were measured in 1933 patients from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Anchors included the St. George’s Respiratory Questionnaire (SGRQ), European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) and EQ visual analogue scale (EQ-VAS), percent-predicted forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), and 6-min walk distance (6MWD). Concurrent validity, internal consistency, ceiling and floor effects, and responsiveness were assessed, followed by estimation of the MID by anchor-based (linear regression) and distribution-based methods (standard error of measurement).ResultsThe UCSDSOBQ had a high level of internal consistency (Cronbach’s alpha = 0.97), no obvious floor or ceiling effect, strong correlations with SGRQ, EQ-5D-5L, and EQ-VAS (|r| > 0.5), and moderate correlations with FVC%, DLCO%, and 6MWD (0.3 < |r| < 0.5). The MID estimate for UCSDSOBQ was 5 points (1–8) for the anchor-based method, and 4.5 points for the distribution-based method.ConclusionThis study demonstrates the validity of UCSDSOBQ in a large and heterogeneous population of patients with fibrotic ILD, and provides a robust MID estimate of 5–8 points.

Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is a major prognostic determinant. However, evidence for its prognostic strength is mainly based on the results of small cohort studies with statistical limitations. This retrospective study, which included 108 patients with a first episode of AE-IPF, aimed to identify prognostic factors and to develop prognostic classification models. Multivariate Cox regression analysis revealed that a lower percent-predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and a lower PaO2/FiO2 ratio at AE onset were independent mortality predictors. If the value of each predictor was lower than the cutoff determined by receiver-operating characteristic analysis, 1 point was assigned. Classification of patients into mild, moderate, and severe groups based on total score showed post-AE 90-day cumulative survival rates of 83.3%, 66.2%, and 22.2%, respectively (model 1: C-index 0.702). Moreover, a decision tree-based model was created with the recursive partitioning method using baseline %FVC and PaO2/FiO2 ratio at AE onset from among multivariable; accordingly, patients were classified into 3 groups with post-AE 90-day cumulative survival rates of 84.1%, 64.3%, and 24.0%, respectively (model 2: C-index 0.735). These models can guide clinicians in determining therapeutic strategies and help design future studies on AE-IPF.

Atopy and pulmonary function among healthy-weight and overweight/obese children with asthma.

Epidemiologic studies have found low/absence of atopy in obese asthmatic children, but the association or lack thereof of atopy with disease morbidity, including pulmonary function, in obese asthma is not well understood. We sought to define the association of atopy with pulmonary function in overweight/obese minority children with asthma. In a retrospective chart review of 200 predominantly minority children evaluated at an academic Pediatric Asthma Center over 5 years, we compared the prevalence of atopy, defined as 1 positive skin prick test or serum-specific immunoglobulin E quantification to environmental allergens, and its association with pulmonary function in overweight/obese (body mass index [BMI] > 85th percentile) (n = 99) to healthy-weight children (BMI, 5th-85thpercentile for age) (n = 101). In a cohort comprised of 47.5% Hispanics and 39.5% African Americans, 81% of overweight/obese and 74% of healthy-weight children were atopic. While atopic healthy-weight children had lower percent-predicted forced expiratory volume in the first second (FEV1 ) (93 ± 13.6 vs 107% ± 33.2%, P = .03) and lower percent-predicted forced vital capacity (FVC) (93% ± 12.2% vs 104% ± 16.1%, P = .01) as compared to nonatopic children, atopy was not associated with FEV1 (P = .7) or FVC (P = .17) in overweight/obese children. Adjusting for demographic and clinical variables, atopy was found to be an independent predictor of FEV1 and FVC in healthy-weight (β = -2.4, P = .07 and β = -1.7, P = .04, respectively) but not in overweight/obese children (β = .6, P = .5 and β = .8, P = .3). Atopy is associated with lower lung function in healthy-weight asthmatics but not in overweight/obese asthmatics, supporting the role of nonallergic mechanisms in disease burden in pediatric obesity-related asthma.

Blood pressure, spirometry, and indoor fine particulate matter in homes heated by wood stoves: pre-intervention results from the EldersAIR randomized trial

Background/Aim: Household air pollution from burning biomass fuels can lead to high concentrations of indoor fine particulate matter (PM2.5) and is associated with many adverse health outcomes. Household heating using wood stoves is common in rural American Indian (AI) communities; however, research on the associations between PM2.5 and health in such communities is limited. Our aims were to assess PM2.5 concentrations and indicators of cardiopulmonary health in older AI adults who use wood stoves for heating, and to evaluate the feasibility of interventions (i.e., education and air filtration) that lower household levels of PM2.5.Methods: EldersAIR was a three-arm pre-post randomized trial in wood stove households from a Northern Rocky Mountain Reservation (n=68) and a Southwestern United States Reservation (n=76). Here, we present pre-intervention concentrations of indoor PM2.5 measured over 2-day sampling periods and measures of peripheral systolic and diastolic blood pressure (SBP; DBP), forced vital capacity (FVC), and forced expiratory volume (FEV1) in older adults.Results: In preliminary analyses, the mean indoor PM2.5 concentration was 38 µg/m3 (standard deviation [sd]=85, median=10) across all homes; 43% of homes had mean PM2.5 concentrations &gt;= 25 µg/m3. Participants were 69 years of age on average (sd=9) with mean body mass index of 30 kg/m2 (sd=6). Participants had mean SBP of 138 mmHg (sd=20) and mean DBP of 77 mmHg (sd=13); 46% had stage-2 hypertension (SBP&gt;=140 or DBP&gt;=90). Mean percent-predicted FVC for participants was 79% (sd=16) and mean percent-predicted FEV1 was 85% (sd=20); 30% had FEV1/FVC ratio &lt; 0.7 or percent-predicted FEV1 &lt; 75%.Conclusions: We observed elevated PM2.5 concentrations inside rural AI homes that used wood stoves for heating. Participants had high SBP and low percent-predicted FVC and FEV1. Our findings highlight the need for interventions that reduce indoor air pollution in an effort to improve health in AI communities.