FEV1 Percent Research Articles

Clinical Remission Predictors in Non-Colonized Bronchiectasis and Severe Asthma with Type 2-Targeted Biologic Therapy: A Retrospective Real-Life Pilot Study

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population.

Antibiotic Therapy in Asthma as One of First Step Treatment, a Phase 3 Randomized Clinical Trial

Background: Focus of this study was on subjects suffering from new onset asthma, but actually, they may involve with an infection. Objectives: The target of this study was to determine the frequency of total control of asthma in new onset asthma. Methods: this is a phase 3 randomized clinical trial. The participants were 50 new onset asthma, who feel suffering from respiratory infection, however the physician diagnosis was asthma according to wheezy chest, spirometry and clear chest roentgenogram. Age less than 18 years and pregnant women were excluded. The subjects were randomly divided into two groups, doxycycline hyclate and the placebo arms. The drugs were repacked in similar in shape container. Primary endpoint was time to first recurrence. Secondary endpoints were frequency of total control of asthma, dyspnea, cough, asthma control test (ACT) score, FEV1, FEV1/FVC, eosinophil and neutrophil in blood and sputum. Results: The difference of clinical findings between two groups before the trial were not significant. Ten percent reported acute attack of asthma during last two months. Treatment with Doxycyline revealed significant improvement of clinical findings, asthma attack and ACT score after two months of treatment, however, complete resolution of clinical findings were significantly higher in Doxycyline group compare to placebo. Clinical findings and FEV1 percent predicted in Doxycyline group T2low asthma group showed significant improvement which were not depicted in T2high group. Eighteen months follow up of the subjects showed complete resolution of asthma symptoms in 12 (48%) on Doxycyline group, which was significantly higher than control group (5 (20%). Time to first exacerbation in doxycycline group was 13.6±5.64 months which was significantly longer than control group (7.49±6.95, P=0.002). Time to first exacerbation in CRP positive was significantly longer (13.64±5.35 months) than CRP negative subjects (9.67±7.76 months, P=0.02). Conclusion: Doxycycline is an effective antibiotic for preventing recurrence of asthma, in selected new subjects who suspicious for respiratory infection.

Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.

Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice. To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality. In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality. Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28). A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.

Clinical phenotypes of sarcoidosis using cluster analysis: a Spanish population-based cohort study.

Sarcoidosis is a clinically heterogenous disease. The objective of this study is the identification of clinical phenotypes using cluster analysis. A model-based clustering relaying on 19 clinical variables was performed in a retrospective cohort of 342 sarcoidosis patients, diagnosed and followed-up from 1999 to 2019 in a tertiary hospital at Northern Spain. Chi-square test and ANOVA were used to compare categorical and continuous variables among groups. Two-sample t-tests and the partition of Pearson's chi-square statistic were used in pairwise comparisons. The Wasfi severity score was calculated and compared among clusters. Cluster analysis identified five groups: C1 (16.1%), C2 (14.3%), C3 (24.3%), C4 (5.0%), and C5 (40.4%). Lung involvement was predominant, ranging from 55.1% (C2) to 100% (C1 and C4). Extrapulmonary involvement was significantly higher in C2 (96.4%) and C3 (98.0%). A significant lower FEV1 percent predicted was detected in C5 (90.5±21.8) versus C1 (102.0±22.9), C3 (102.3±17.6) and C4 (105.8±20.8). The cluster 5 had a lower FVC percent predicted (96.6±18.9) than others, ranging from 108.1±18.0 (C3) to 111.5±21.7 (C4). The prescription of systemic glucocorticoids and non-corticosteroid immunosuppressants was higher in the clusters 1, 3 and 5. Chronicity rates were higher in C3 (31.3%) and C5 (32.6%) compared to C1 (9.1%) and C4 (0%), as well as the Wasfi severity score values. Five phenotypes with different clinical and prognostic characteristics are proposed in our study. Cluster analysis can be a useful tool for identifying clinical patterns in a disease as heterogeneous as sarcoidosis and optimising its management.

Spirometry findings of chronic lung disease in high-altitude residents of Ladakh (>11000 feet above sea level)

Ladakh is a hilly Himalayan dry desert, situated at an altitude of >11000 feet. Studies have demonstrated that the spirometric values of high-altitude residents are significantly higher than those of low-landers. This is a retrospective observational study that analyzes the spirometry pattern in chronic lung diseases among people from Ladakh. Enrolled subjects were clinic-radiologically diagnosed and had at least one spirometry report. The spirometric parameters were analyzed for normal and abnormal patterns of lung function. The abnormal patterns were further classified into types of ventilator defects and their severity. A total of 122 cases were included, with 67 (55%) men. The mean age was 52.2±15.4 years. The most common diseases were chronic obstructive pulmonary disease (COPD) in 51 cases (41%), and asthma in 41 (33%). The median predicted percentage of forced vital capacity (FVC) was 116% (63-179%) with >100% in 105 (85%) patients. The median predicted percentage of the forced expiratory volume in the 1st second (FEV1) was 113% (99-175%) with >100% in 90 (74%) patients. FVC was reduced in 9 (7%) cases, normal in 62 (51%), and more than normal in 49 (42%), with 11 (9%) cases having >150% of the predicted percentage. FEV1 was reduced in 9 (8%) cases, normal in 67 (55%), and more than normal in 46 (37%) cases, with >150% predicted seen in 10 (8%) cases. Similarly, overall, the predicted percentages of both FVC and FEV1 were >100% in all obstructive airway diseases as well as in the separate COPD and asthma subgroups. FVC and FEV1 amongst chronic lung disease patients from Ladakh were more than normal in the majority. These higher values of spirometry led to incorrect disease severity classifications and disease patterns. We propose that studies should be done to devise local reference equations for spirometry for Himalayan high-altitude residents of India.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

CT Chest Imaging Using Normalized Join-Count: Predicting Emphysema Progression in the CanCOLD Study.

Background Pre-existing emphysema is recognized as an indicator of future worsening in patients with chronic obstructive pulmonary disease (COPD) when observed through CT imaging. However, it remains uncertain whether additional factors, such as the spatial compactness of CT emphysema, might also serve as predictors of disease progression. Purpose To evaluate the relationship between the compactness of CT emphysema voxels and emphysema progression. Materials and Methods This secondary analysis uses data from the prospective Canadian Cohort Obstructive Lung Disease (CanCOLD) study, examining CT images obtained in participants with and without COPD at baseline and a 3-year follow-up time point (November 2009 to November 2018). Measurements of forced expiratory volume in first second of expiration (FEV1) and diffusing capacity of lung for carbon monoxide (DLco) were collected. The normalized join-count (NJC) measurement from baseline CT images and lung density (LD) changes were analyzed. Emphysema progression was defined as an annualized LD change of less than half an SD below the mean of the participants without COPD with no smoking history. Multivariable linear and logistic regression models were used to assess the association between baseline CT NJC measurements and the annualized change in LD, FEV1, DLco, and emphysema progression versus nonprogression. Results A total of 524 participants (mean age, 66 years ± 10 [SD]; 293 male) (FEV1 percent predicted, 88% ± 19; FEV1/FVC, 67% ± 9; DLco percent predicted, 105% ± 25) were analyzed, 187 (36%) of whom had COPD. CT NJC was associated with the annualized change in LD (P < .001), FEV1 (P = .02), and DLco (P = .01). Additionally, CT NJC predicted emphysema progression versus nonprogression (odds ratio, 2.24; 95% CI: 1.37, 3.50; P < .001). Conclusion The spatial distribution, or "compactness," of CT emphysema voxels predicted emphysema progression in individuals with and without COPD. ClinicalTrials.gov Identifier: NCT00920348 © RSNA, 2024 Supplemental material is available for this article.

Mental health, sleep, and respiratory health after initiating elexacaftor/tezacaftor/ivacaftor treatment in children with cystic fibrosis

AbstractIntroductionCystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function but its effect on mental health and sleep remains poorly understood. We report on mental health, sleep, and respiratory health outcomes of adolescents with CF commenced on ETI therapy, and monitored the prevalence of neuropsychiatric issues through the coronavirus disease 2019 pandemic.MethodsWe conducted a prospective longitudinal study of 31 adolescents (aged 10–18 years) from July 2021 to October 2022. Data collected include demographics, Patient Health Questionnaire‐9 (PHQ‐9), General Anxiety Disorder‐7 (GAD‐7), Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC) scores, and FEV1 percent predicted. Twenty of 31 adolescents had data before and after ETI initiation. Mean differences (MD) in mental health, sleep, and respiratory health pre‐ and post‐ETI therapy commencement were estimated using paired t‐tests. The prevalence and trajectories of anxiety, depression, and sleep disturbance were described between the ETI epochs, and over the pandemic period.ResultsFEV1 improved following ETI therapy commencement (MD, 95% confidence interval [CI]: 7.1% (4.7%–9.6%) whereas PHQ‐9, GAD‐7, PDSS, and SDSC scores did not change significantly. Ten percent of participants developed new‐onset anxiety/depression concerns and 10% developed new sleep concerns following ETI initiation.ConclusionThis is the first prospective longitudinal study of mental health and sleep changes after ETI commencement in adolescents with CF. Although respiratory outcomes improved, ETI did not improve anxiety, depression or sleep.

Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts

ObjectivesTo investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. Study designWe analyzed data from two multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (FEV1 z-score≤-1.645) as per 2022 ATS guidelines. ResultsCompared with the race-specific GLI, the race-neutral equation yielded increases in the median FEV1 and FVC percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21% and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; p<0.001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; p=0.001). Results were similar across both cohorts. ConclusionsAs there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

The impact of switching to race-neutral reference equations on FEV1 percent predicted among people with cystic fibrosis,

RationaleThe American Thoracic Society recommended switching to race-neutral spirometry reference equations, as race is a social construct and to avoid normalizing disparities in lung function due to structural racism. Understanding the impact of the race-neutral equations on percent predicted forced expiratory volume in one second (ppFEV1) in people with cystic fibrosis (PwCF) will help prepare patients and providers to interpret pulmonary function test results. Objective(s)To quantify the impact of switching from Global Lung Initiative (GLI) 2012 race-specific to GLI 2022 Global race-neutral reference equations on the distribution of ppFEV1 among PwCF of different races. MethodsCross-sectional analysis of FEV1 among PwCF ages ≥6 years in the 2021 U.S. Cystic Fibrosis Foundation Patient Registry. We describe the absolute difference in ppFEV1 between the two reference equations by reported race and the effect of age and height on this difference. ResultsWith the switch to GLI Global, ppFEV1 will increase for White (median increase 4.7, (IQR: 3.1; 6.4)) and Asian (2.6 (IQR: 1.6; 3.7)) individuals and decrease for Black individuals (-7.7, (IQR: -10.9; -5.2)). Other race categories will see minimal changes in median ppFEV1. Individuals with higher baseline ppFEV1 and younger age will see a greater change in ppFEV1 (i.e., a greater improvement among White and Asian individuals and a greater decline among Black individuals). ConclusionsSwitching from GLI 2012 race-specific reference equations to GLI 2022 Global race-neutral equations will result in larger reductions in ppFEV1 among Black individuals with CF than increases among White and Asian people with CF.

Association Between FEV₁ Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical Trial of Inhaled Liposomal Cyclosporine Plus Standard-of-Care Versus Standard-of-Care Alone for Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND The association between forced expiratory volume in 1 second (FEV1) trajectory and mortality in bronchiolitis obliterans syndrome (BOS) is not well defined. Using long-term data from a prior clinical trial of inhaled liposomal cyclosporine A (L-CsA-I) for lung transplant patients with BOS, this study examined the association between longitudinal FEV₁ change and mortality. MATERIAL AND METHODS We analyzed long-term data from a clinical trial which randomized 21 patients with BOS (³20% decrease in FEV1 from personal maximum) to receive L-CsA-I plus standard-of-care (n=11) or standard-of-care (SOC) alone (n=10) for 24 weeks. A joint statistical model, combining a linear mixed model for FEV₁ change and Cox regression for mortality, was utilized to examine the overall association between FEV₁ trajectory and mortality during follow-up. RESULTS The 21 trial participants (10 single, 11 double lung recipients) had a mean FEV₁ of 1.7±0.6 Liters at randomization. Median follow-up post-randomization was 35 months. In joint model analysis, 1 percent FEV₁ decline predicted 1.076-fold increased mortality risk (95% confidence interval: -0.998 to 1.160, p=0.058). FEV₁ decline was reduced by 2.6% per year in L-CsA-I patients compared to SOC (p=0.210), and overall survival at 1/3/5 years was 91%/64%/27% vs 90%/20%/0% for L-CsA-I versus SOC, respectively (p=0.164). CONCLUSIONS In BOS patients, greater longitudinal FEV₁ decline predicts increased mortality. Trends towards prolonged stabilization of FEV₁ and improved survival were observed with L-CsA-I receipt. Further analyses will aid in evaluating the utility of FEV₁ change as a survival predictor, having implications in BOS management and future trial design.

Understanding changes in pulmonary function and functional status in breast cancer patients after systemic chemotherapy and radiotherapy: a prospective study

BackgroundRespiratory complications in breast cancer (BC) patients after chemotherapy (CT) and radiotherapy (RT) have been well acquainted and these complications should be investigated to prevent secondary problems and/or improve BC patients’ clinical outcomes. Therefore, this study aimed to assess the potential acute effect of systemic chemotherapy and radiotherapy on respiratory function and functional status of patients with breast cancer.MethodsA total of 25 BC patients who were candidates for systemic chemotherapy and radiotherapy were recruited after oncological examination and included in this study. Respiratory function and functional status were assessed with the Pulmonary Function Test (PFT) and the Six-Minute Walk Test (6MWT), respectively. Patients were assessed before CT (c0), after CT (c1), and after RT (r1).Results25 BC patients were assessed in c0 and c1 while only 15 out of 25 patients (60%) were assessed in r1. The actual values of Forced vital capacity (FVC) (t = 2.338, p =.028), Forced expiratory volume in 1s (FEV1 (t = 2.708, p =.012), and the forced expiratory flow of between 25% and 75% of vital capacity (FEF25-75%) (t = 2.200, p =.038) were found significantly different after systemic CT. Inspiratory (MIP) and expiratory (MEP) muscle strength also did not show a significant change from c0 to c1. A significant effect of the type of surgery was found (Wilks’ lambda, F [1, 19] = 6.561, p =.019, ηp2 = 0.25) between c0 and c1 in actual FVC value. The main effect of time was found significant in FVC (F [2, 28] = 4.840, p =.016, ηp2 = 0.25) from c0 to r1. Pairwise comparisons with Bonferroni correction showed that there was a significant difference between c0 and r1 (p =.037).DiscussionThe present study showed decreased FVC and FEV1 actual values and percent predicted rates from baseline to the completion of treatment. Since the interactional effect of the type of surgery was significant, we suggest that clinical and demographic factors such as age should be considered when interpreting the early changes in PFT. In addition, the significant linear trend of decreasing in some specific outcomes in respiratory function also highlighted the need for continuous monitoring of potential respiratory problems in patients with BC from baseline to the completion of chemotherapy and radiotherapy.

Multidisciplinary diagnosis and treatment model based on a retrospective cohort study: Pulmonary function and prognosis quality of life in severe COPD.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worsening airflow limitation. To explore pulmonary function rehabilitation, life quality and prognosis in patients with severe COPD. Between February 2018 and August 2021, 150 patients with severe COPD cured in our hospital were arbitrarily assigned into the control group (n= 75) and study group (n= 75). The control group received routine treatment and the research group received multidisciplinary diagnosis and treatment. The body mass index, airflow obstruction, dyspnea and exercise (BODE), pulmonary function, the number of acute attacks, 6-minute walking distance (6MWD), Borg score and life quality were compared. There was no remarkable difference in BODE score before treatment (P> 0.05). During the 2- and 6-month following treatment, the BODE score of the study group was lower (P< 0.05). In the study group, FEV1 percentage of the predicted value, forced expiratory volume in one second (PPO-FEV1) and the percentage of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) in the first second were higher (P< 0.05). In the study group, there were fewer acute attacks (P< 0.05). After treatment, the 6MWD of the study group following 2- and 6-month treatment was higher (P< 0.05). The Borg scores of the study group at 2- and 6-months after treatment were lower (P< 0.05). There were no remarkable differences in the score of life quality before treatment (P> 0.05), however, the symptom score, activity score, influence score and total score of the study group were lower after the treatment (P< 0.05). The application of multidisciplinary diagnosis and treatment model can promote the rehabilitation of pulmonary function of patients with severe COPD, improve their prognosis, slow down the development of the disease and enhance their life quality.

Pulmonary Function in People Living With Human Immunodeficiency Virus: A Meta-Analysis

BackgroundHIV can infect bronchial epithelial cells rendering individuals susceptible to lung damage. Our objective was to determine the effects of human immunodeficiency virus (HIV) infection on pulmonary function tests. MethodsWe performed a meta-analysis after conducting a literature search in PubMed, Embase, Cochrane Library and Virtual Health Library databases from inception to December 31st, 2022. We employed the inverse variance method with a random effects model to calculate the effect estimate as the mean difference (MD) and 95% confidence interval (CI). We calculated the heterogeneity with the I2 statistic and performed a meta-regression analysis by age, sex, smoking, CD4 T-cells count and antiretroviral therapy. We also conducted a sensitivity analysis according to the studies’ publication date, and excluding the study with the greatest weight in the effect. The PROSPERO registry number was CRD42023401105. ResultsThe meta-analysis included 20 studies, with 7621 living with HIV and 7410 control participants. The pooled MD (95%CI) for the predicted percentage of FEV1, FVC and DLCO were −3.12 (−5.17, −1.06); p=0.003, −1.51 (−3.04, 0.02); p=0.05, and −5.26 (−6.64, −3.87); p<0.001, respectively. The pooled MD for FEV1/FVC was −0.01 (−0.02, −0.01); p=0.002. In all cases, there was a considerable heterogeneity. The meta-regression analysis showed that among studies heterogeneity was not explained by patient age, smoking, CD4 T-cells count or antiretroviral therapy. ConclusionPulmonary function tests are impaired in people living with HIV, independently of age, smoking, CD4 T-cells count, and geographical region.

Normal Lung Function and Mortality in World Trade Center Responders and National Health and Nutrition Examination Survey III Participants.

Rationale: Low FEV1 is a biomarker of increased mortality. The association of normal lung function and mortality is not well described. Objectives: To evaluate the FEV1-mortality association among participants with normal lung function. Methods: A total of 10,999 Fire Department of the City of New York (FDNY) responders and 10,901 Third National Health and Nutrition Examination Survey (NHANES III) participants, aged 18-65 years with FEV1 ⩾80% predicted, were analyzed, with FEV1 percent predicted calculated using Global Lung Function Initiative Global race-neutral reference equations. Mortality data were obtained from linkages to the National Death Index. Cox proportional hazards models estimated the association between FEV1 and all-cause mortality, controlling for age, sex, race/ethnicity, smoking history, and, for FDNY, work assignment. Cohorts were followed for a maximum of 20.3 years. Measurements and Main Results: We observed 504 deaths (4.6%) of 10,999 for FDNY and 1,237 deaths (9.4% [weighted]) of 10,901 for NHANES III. Relative to FEV1 ⩾120% predicted, mortality was significantly higher for FEV1 100-109%, 90-99%, and 80-89% predicted in the FDNY cohort. In the NHANES III cohort, mortality was significantly higher for FEV1 90-99% and 80-89% predicted. Each 10% higher predicted FEV1 was associated with 15% (hazard ratio, 0.85; 95% confidence interval, 0.80-0.91) and 23% (hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) lower mortality for FDNY and NHANES III, respectively. Conclusions: In both cohorts, higher FEV1 is associated with lower mortality, suggesting higher FEV1 is a biomarker of better health. These findings demonstrate that a single cross-sectional measurement of FEV1 is predictive of mortality over two decades, even when FEV1 is in the normal range.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing

BackgroundSome patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing.ObjectiveTo determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT).MethodsUsing random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated.ResultsOf 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered ‘yes’ to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72–0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT.ConclusionsFour readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

Controlling Nutritional Status Score as a Predictor for Chronic Obstructive Pulmonary Disease Exacerbation Risk in Elderly Patients.

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to assess poor nutritional status as well as to predict clinical adverse outcomes in different clinical settings. No data are available in older patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the CONUT score as a predictor of frequent exacerbations. We retrospectively enrolled 222 patients aged 65 years or older, classified in two groups according to the number of exacerbations (or hospitalizations because AECOPD) during the previous year. The two groups were further divided according to low (<5) or high (≥5) CONUT scores. A total of 67.2% of frequent exacerbators had a high CONUT score. These patients exhibited a significantly higher CAT score, lower FEV1 percentage value, and higher prevalence of severe GOLD stages compared to those with low CONUT. Multivariate analysis showed that a CONUT score ≥ 5 was the best independent predictor (OR 20.740, p < 0.001) of the occurrence of ≥2 exacerbations (or 1 hospitalization) during the previous year. The CONUT score seemed to have a high prognostic value for frequent exacerbations for COPD in older patients. The predictive role of different CONUT score cut-off values needs to be validated in larger COPD populations in future multi-center, prospective clinical studies.

The indirect effects of socioeconomic position on lung function: a mediation analysis

Abstract Background There is a strong link between socioeconomic position and pulmonary health, but less is known about their connecting pathways. We analyzed the direct and indirect effects of education and deprivation on lung function using air pollutants in a mediation framework. Methods We used spirometry tests, demographic, and health information on 5703 Czechs, with a mean age of 58.3 ± 7.1 years from the Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study between 2002 to 2005. The annual means of particulate matter 10 (PM10), particulate matter 2.5 (PM2.5), and nitrogen dioxide (NO2) estimated by Shen et al. (2022) for the years 2000 to 2003 were matched to the geographic addresses of the participants. Multiple mediation analyses assessed the relationship between socioeconomic variables (education and deprivation) and the predicted percentage of Forced Expiratory Volume in the first second (FEV1) and the role of mediators: PM10 or PM2.5 or NO2, smoking behavior, and body mass index (BMI). The models were adjusted for sex, age. Results 9.27% of individuals had &amp;lt;70% of the predicted percentage of FEV1. We tested the first model using PM10, smoking, and BMI as mediators. We found significant indirect effects from education through PM10 (β = 0.17, CI95%: 0.10-0.25), BMI (β = 0.36, 0.25-0.47), and smoking (β = 0.17, 0.08-0.25) with indirect effects explaining 34% of the total effect of education. The indirect effect of deprivation was significant only through smoking (β=-0.11, -0.14 to -0.07), explaining 31% of the effect of deprivation. Similar results were observed when we tested a second model using PM2.5 instead of PM10, and a third model including NO2 instead of PM10. Conclusions Air pollutants seem to mediate the association between education and lung function, but not between deprivation and lung function, however, further research is needed to confirm our findings. Key messages • Higher education appears to be associated with better environmental factors that prevent loss of lung function. • Most of the routes that connect socioeconomic factors and lung function remain unclear.

O028 Worsened sleep and mood after initiating elexacaftor/tezacaftor/ivacaftor treatment in children with cystic fibrosis

Abstract Background CFTR modulator Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function and but its effect on mental health and sleep remains poorly understood. We report sleep, mood and respiratory health outcomes of adolescents with CF with ETI therapy. Methods We conducted a prospective longitudinal study of 31 adolescents (aged 10 to 18 years) from July 2021 to October 2022. Data collected include demographics, pediatric daytime sleepiness scale (PDSS), sleep disturbance scale for children (SDSC), patient health questionnaire-9 (PHQ-9), generalised anxiety disorder-7 (GAD-7) scores and FEV1 percent predicted. Results Paired-T testing demonstrated a significant improvement in FEV1, whereas PDSS, PHQ-9, and GAD-7 scores worsened following ETI therapy, but did not reach statistical significance. SDSC scores marginally reduced. Ten percent of participants developed new onset sleep concerns and new mood concerns developed in 10% following ETI initiation. Conclusion/Outcome This is the first prospective longitudinal study of sleep and mood changes with ETI in adolescents with CF. ETI does not improve sleep and mood in the same way as respiratory health outcomes.