Poor Lung Function Research Articles

Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma

Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants. We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n=660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n=1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and SNPs in their target genes. Statistical significance was determined using an false discovery rate-adjusted Q-value. The top metabolite principal component, PCLF, was significantly associated with better LFTs after multiple-testing correction (Q-value=0.03). PCLF is composed of the urea cycle, caffeine, corticosteroid, carnitine, and potential microbial (secondary bile acid, tryptophan, linoleate, histidine metabolism) metabolites. Higher levels of PCLF were also associated with increases in lung function measures and decreased circulating neutrophil percentage in both CAMP and GACRS. PCLF was also significantly associated with microRNA miR-143-3p, and SNPs in three miR-143-3p target genes; CCZ1 (P-value=2.6×10-5), SLC8A1 (P-value=3.9×10-5); and TENM4 (P-value=4.9×10-5). This study reveals associations between metabolites, miR-143-3p and LFTs in children with asthma, offering insights into asthma physiology and possible interventions to enhance lung function and long-term health. Molecular data for CAMP and GACRS via the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung, and Blood Institute (NHLBI).

A study to assess the relationship between vitamin D3 levels and the risk of acute exacerbation in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of mortality worldwide. Vitamin D deficiency in COPD has been associated with poor lung function and decreased muscle power, which further increases the risk of exacerbations. The role of vitamin D in preventing acute exacerbations of COPD has conflicting results in the literature. Hence, we planned this study to assess the relationship between vitamin D3 levels and the risk of acute exacerbations among COPD patients in a tertiary care center in north India. This was a prospective randomized control trial that was performed on 100 consecutive stable COPD patients attending the Department of Respiratory Medicine at Maharishi Markandeshwar Medical College and Hospital, Solan, India. The patients with subnormal vitamin D3 levels (i.e., less than 30 ng/mL) were divided into the intervention and control groups. Baseline demographic profiles, lung function, COPD assessment test (CAT) score, modified Medical Research Council grade and chest radiology were performed and repeated after 12 months in all these patients. All these parameters were recorded and compared with the baseline values obtained at the beginning of the study. Out of 100 subjects, 96 had vitamin D deficiency, of which 48 were assigned to the intervention group and 48 to the control group. Among the 100 subjects, 74 (74%) were males and 26 (26%) were females, with a mean age of 66.9±9.4 years. The mean vitamin D level was 14.71±6.69 in these 96 patients. The vitamin D level improved after 3 months of supplementation to the mean level of 45.56±16.18 in the intervention group. Vitamin D supplementation was positively correlated with a decrease in the rate of acute exacerbations in the intervention group in terms of reduction in mean CAT score (4.17 in intervention and 1.43 in non-interventional group, p<0.001), number of acute exacerbations (1.7 in intervention and -1.05 in non-interventional group, p<0.001), and number of emergency visits (p=0.0121) during the 9-month period after attainment of a normal vitamin D level. Vitamin D supplementation plays a key role in COPD patients with D3 hypovitaminosis in decreasing COPD acute exacerbations, improving the CAT score, and reducing the number of emergency visits.

Factors related to lung function outcomes in critically ill COVID-19 patients in South Korea.

New variants of the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic continue to emerge. However, little is known about the effect of these variants on clinical outcomes. This study evaluated the risk factors for poor pulmonary lung function test (PFT). The study retrospectively analyzed 87 patients in a single hospital and followed up by performing PFTs at an outpatient clinic from January 2020 to December 2021. COVID-19 variants were categorized as either a non-delta variant (November 13, 2020-July 6, 2021) or the delta variant (July 7, 2021-January 29, 2022). The median age of the patients was 62 years, and 56 patients (64.4%) were male. Mechanical ventilation (MV) was provided for 52 patients, and 36 (41.4%) had restrictive lung defects. Forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO ) were lower in patients on MV. Male sex (odds ratio [OR], 0.228) and MV (OR, 4.663) were significant factors for decreased DLCO . The duration of MV was associated with decreased FVC and DLCO . However, the type of variant did not affect the decrease in FVC (P=0.750) and DLCO (P=0.639). Among critically ill COVID-19 patients, 40% had restrictive patterns with decreased DLCO . The reduction of PFT was associated with MV, type of variants.

Ventilatory capacity in CLAD is driven by dysfunctional airway structure

Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Exvivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. This research was funded with the National research fund Flanders (G060322N), received by R.V.

Environmental Injustice Is Associated With Poorer Asthma Outcomes in School-Age Children With Asthma in Metropolitan Atlanta, Georgia

BackgroundEnvironmental justice mandates that no person suffers disproportionately from environmental exposures. The Environmental Justice Index (EJI) provides an estimate of the environmental burden for each census tract but has not yet been utilized in asthma populations. ObjectiveWe hypothesized that children from census tracts with high environmental injustice determined by the EJI would have a greater burden of asthma exacerbations, poorer asthma control, and poorer lung function over 12 months. MethodsChildren 6-18 years with asthma (N=575) from metropolitan Atlanta, Georgia, completed a baseline research visit. Participant addresses were geocoded to obtain the EJI Social-Environmental ranking for each participant’s census tract, which was divided into tertiles. Medical records were reviewed for 12 months for asthma exacerbations. A subset of participants completed a second research visit involving spirometry and questionnaires. ResultsCensus tracts with the greatest environmental injustice had more racial/ethnic minorities, lower socioeconomic status, more hazardous exposures (particularly to airborne pollutants), and greater proximity to railroads and heavily trafficked roadways. Children with asthma residing in high injustice census tracts had a longer duration of asthma, greater historical asthma-related healthcare utilization, poorer asthma symptom control and quality of life, and more impaired lung function. By 12 months, children from high injustice census tracts also had more asthma exacerbations with a shorter time to exacerbation and persistently more symptoms, poorer asthma control, and reduced lung function. ConclusionDisparities in environmental justice are present in metropolitan Atlanta that may contribute to asthma outcomes in children. These findings require additional study and action to improve health equity.

Clinical characteristics of obese, fixed airway obstruction, exacerbation-prone phenotype and comorbidities among severe asthma patients: a single-center study

BackgroundSevere asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear.MethodsA retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study.ResultsA total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations.ConclusionThe existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Efficient designs and analysis of two-phase studies with longitudinal binary data.

Researchers interested in understanding the relationship between a readily available longitudinal binary outcome and a novel biomarker exposure can be confronted with ascertainment costs that limit sample size. In such settings, two-phase studies can be cost-effective solutions that allow researchers to target informative individuals for exposure ascertainment and increase estimation precision for time-varying and/or time-fixed exposure coefficients. In this paper, we introduce a novel class of residual-dependent sampling (RDS) designs that select informative individuals using data available on the longitudinal outcome and inexpensive covariates. Together with the RDS designs, we propose a semiparametric analysis approach that efficiently uses all data to estimate the parameters. We describe a numerically stable and computationally efficient EM algorithm to maximize the semiparametric likelihood. We examine the finite sample operating characteristics of the proposed approaches through extensive simulation studies, and compare the efficiency of our designs and analysis approach with existing ones. We illustrate the usefulness of the proposed RDS designs and analysis method in practice by studying the association between a genetic marker and poor lung function among patients enrolled in the Lung Health Study (Connett et al, 1993).

Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Rationale: Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. Objectives: To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear. Methods: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n = 280), including the international multicenter cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) study (n = 251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing Pseudomonas aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing, and the bronchiectasis resistome was evaluated in association with clinical outcomes and underlying host microbiomes. Measurements and Main Results: The bronchiectasis resistome features a unique resistance gene profile and increased counts of aminoglycoside, bicyclomycin, phenicol, triclosan, and multidrug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles, including increased macrolide and multidrug resistance genes, associate with shorter intervals to the next exacerbation, whereas distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant "resistotypes," RT1 and RT2, the latter characterized by poor clinical outcomes, increased multidrug resistance, and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favorable resistome profile demonstrating reduced resistance gene diversity. Conclusions: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis resistotypes link to clinical disease and are modifiable through targeted antimicrobial therapy.

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz &gt; upper limit of normal or respiratory system reactance at 5 Hz &lt; lower limit of normal. The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p&lt;0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p&lt;0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p&lt;0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p&lt;0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

Comparison of Robotic and Open Lobectomy for Lung Cancer in Marginal Pulmonary Function Patients: A Single-Centre Retrospective Study.

The treatment of non-small-cell lung cancer (NSCLC) patients with reduced respiratory function represents a challenge for thoracic surgeons. Minimally invasive surgery seems to be beneficial for these patients because it reduces tissue trauma and its impact on respiratory mechanics. Application of the robotic technique, the use of CO2 insufflation and longer surgical time are factors that could influence the outcomes of marginal pulmonary function patients. The objective of this study was to evaluate the impact of the robotic technique on the postoperative outcomes of patients with poor lung function. We retrospectively collected and analyzed data from consecutive marginal respiratory function patients who underwent robotic or open lobectomy for NSCLC. Data regarding clinical, operative and postoperative details were compared between the open and robotic approaches. The outcomes of 100 patients with reduced respiratory function were evaluated, of whom 59 underwent open lobectomies and 41 underwent robotic lobectomies. Robotic lobectomy was characterized by a longer operative time, a reduced hospital stay and a lower incidence of postoperative complications (22% vs. 33.9%), when compared to the open approach. Robotic lobectomy is a safe and feasible procedure for patients with marginal pulmonary function.

Perioperative Management Challenges for Post-Tuberculous Stage-III Empyema with Massive Pneumothorax Mimicking Vanishing Lung Syndrome: A Case Report

Surgical resection is frequently the intervention required for post-tuberculous empyema or other sequels. However, pneumonectomy may not be feasible in some situations, and video-assisted thoracoscopic surgery (VATS) plays a role in such a scenario. Whether a patient undergoes open resection of VATS, isolation of infected lung is integral to one-lung ventilation and better access to the surgical field, and a double-lumen tube (DLT) remains the preferred choice. Difficulties in DLT placement after pneumonectomy are reported; however, failure to isolate a lung by appropriately placed DLT is scarce or absent. A 28-year cachectic gentleman with poor preoperative lung function was suffering from endobronchial tuberculosis. He also had one episode of tuberculosis twelve-year back. At presentation, he had a massive pneumothorax and stage-III empyema as a sequel, including a rare finding of plastered mediastinum mimicking vanishing lung syndrome. He underwent uniportal-VATS under general anesthesia using one-lung ventilation. Complete lung destruction from active tuberculosis and its sequel leading to the plastered mediastinum and deformed airway pose a significant lung isolation challenge. U-VATS can be considered for therapeutic purpose where standard thoracotomy and pneumonectomy is contra-indicated. However, lung isolation in such patients is tricky and poses a risk. The present case highlights the challenges faced with lung isolation using a DLT and discusses the probable remedy to these problems.

Tollip deficiency exaggerates airway type 2 inflammation in mice exposed to allergen and influenza A virus: role of the ATP/IL-33 signaling axis.

Toll-interacting protein (Tollip) is a negative regulator of the pro-inflammatory response to viruses, including influenza A virus (IAV). Genetic variation of Tollip has been associated with reduced airway epithelial Tollip expression and poor lung function in patients with asthma. Whether Tollip deficiency exaggerates type 2 inflammation (e.g., eosinophils) and viral infection in asthma remains unclear. We sought to address this critical, but unanswered question by using a Tollip deficient mouse asthma model with IAV infection. Further, we determined the underlying mechanisms by focusing on the role of the ATP/IL-33 signaling axis. Wild-type and Tollip KO mice were intranasally exposed to house dust mite (HDM) and IAV with or without inhibitors for IL-33 (i.e., soluble ST2, an IL-33 decoy receptor) and ATP signaling (i.e., an antagonist of the ATP receptor P2Y13). Tollip deficiency amplified airway type 2 inflammation (eosinophils, IL-5, IL-13 and mucins), and the release of ATP and IL-33. Blocking ATP receptor P2Y13 decreased IL-33 release during IAV infection in HDM-challenged Tollip KO mice. Furthermore, soluble ST2 attenuated airway eosinophilic inflammation in Tollip KO mice treated with HDM and IAV. HDM challenges decreased lung viral load in wild-type mice, but Tollip deficiency reduced the protective effects of HDM challenges on viral load. Our data suggests that during IAV infection, Tollip deficiency amplified type 2 inflammation and delayed viral clearance, in part by promoting ATP signaling and subsequent IL-33 release. Our findings may provide several therapeutic targets, including ATP and IL-33 signaling inhibition for attenuating excessive airway type 2 inflammation in human subjects with Tollip deficiency and IAV infection.

Pulmonary function and toxicities of proton versus photon for limited-stage small cell lung cancer.

We aimed to compare the oncological outcomes and toxicities of definitive proton beam therapy (PBT) and photon beam therapy in patients with limited-stage small cell lung cancer (LS-SCLC). We retrospectively reviewed 262 patients with newly diagnosed LS-SCLC who underwent definitive PBT (n = 20; proton group) or photon beam therapy (n = 242; photon group) with concurrent chemotherapy between January 2016 and February 2021 and compared overall survival (OS), progression-free survival (PFS), dose-volume parameters, and toxicities between the groups. The median follow-up duration was 24.5 months (range, 3.7 to 78.7). Baseline lung function was significantly worse and clinical target volume (CTV) was larger in the proton group (CTV: 296.6 vs. 215.3 mL; p = 0.080). The mean lung V10 was 37.7% ± 16.8% and 51.6% ± 24.5% in the proton and photon groups, respectively (p = 0.002). Two-year OS and PFS rates were 57.2% and 35.7% in the proton group and 65.3% and 40.8% in the photon group, respectively (p = 0.542 and 0.748, respectively). Grade ≥2 radiation pneumonitis and esophagitis occurred in 5 (25.0%) and 7 (35.0%) PBT-treated patients and 66 (27.3%) and 40 (16.5%) photon beam therapy-treated patients, respectively (p = 0.826 and 0.062, respectively). Although the proton group had poorer lung function and a larger CTV than that in the photon group, both groups exhibited comparable treatment outcomes and radiation-related toxicities in LS-SCLC. PBT may be a valuable therapeutic modality in patients with poor pulmonary function or extensive disease burden owing to its lung-sparing ability.

Environmental pollutants increase the risks of acute exacerbation in patients with chronic airway disease.

Respiratory infections are a common cause of acute exacerbations in patients with chronic airway disease, however, environmental factors such as air pollution can also contribute to these exacerbations. The study aimed to determine the correlation between pollutant levels and exacerbation risks in areas exposed to environmental pollution sources. From 2015 to 2016, a total of 788 patients with chronic airway diseases were enrolled in a study. Their medical records, including hospital visits due to acute exacerbations of varying severity were analyzed. Additionally, data on daily pollutant levels from the Air Quality Monitoring Network from 2014 to 2016 was also collected and analyzed. Patients with chronic airway disease and poor lung function (FEV1 < 50% or obstructive ventilatory defect) have a higher risk of severe acute exacerbations and are more likely to experience more than two severe acute exacerbations within a year. The study found that in areas exposed to environmental pollution sources, there is a significant correlation between NO2, O3, and humidity with the main causes of severe acute exacerbation. When the levels of NO2 were higher than 16.65 ppb, O3 higher than 35.65 ppb, or humidity higher than 76.95%, the risk of severe acute exacerbation in patients with chronic airway disease increased. Acute exacerbations of chronic airway disease can be triggered by both the underlying disease state and the presence of air pollution. Computer simulations and early warning systems should be developed to predict acute exacerbations of chronic airway disease based on dynamic changes in air pollution.

Impact of the COVID-19 pandemic on well-being and quality of life of patients with alpha-1-antitrypsin deficiency

BackgroundAlpha-1-antitrypsin deficiency (AATD) is a genetic disorder characterized by mutations in the SERPINA1 gene, primarily affecting the lungs and liver. The COVID-19 pandemic has raised questions about the susceptibility of individuals with AATD to COVID-19 and whether patients with rare lung disease might experience increased stress-related symptoms and mental health challenges. This study aims to investigate the impact of the COVID-19 pandemic on the quality of life of individuals living with AATD.MethodsThe study enrolled participants from the German registry for individuals with AATD. Questionnaires were sent to the 1250 participants, and a total of 358 patients were included in the analysis. The primary objective was to examine the influence of sociodemographic and disease-related factors on the occurrence of stress-related symptoms. This was accomplished through correlation and regression analyses. We also investigated the role of baseline quality of life (QoL), as measured by the St. George’s Respiratory Questionnaire (SGRQ), as a mediator of this relationship.ResultsStress-related symptoms were predicted by young age, female gender, psychological disorders, and a history of exacerbations of lung disease, as determined by multiple regression analysis. QoL as measured by the SGRQ mediated the relationship between poor lung function, stress, and a decline in overall well-being.ConclusionThe presented data demonstrate that the COVID-19 pandemic significantly affects the psychological well-being of patients with rare diseases, leading to increased levels of anxiety and stress. Disease-related factors can exacerbate stress manifestations, especially when compounded by sociodemographic and contextual factors. Thus, our study emphasizes the crucial role of taking these factors into account when managing individuals with AATD in pandemic situations.

Could Poor Outcomes for Patients with Limited Lung Function Treated with SAbR Necessitate PULSAR?

Stereotactic ablative radiotherapy (SAbR) employs precise targeting and delivery of ablative radiation doses in patients with medically inoperable early-stage non-small cell lung cancer, as well as patients with pulmonary metastases. SAbR is well tolerated with few studies reporting a minimal decline in pulmonary function tests (PFTs). However, poor pulmonary function is considered a risk factor for radiation induced lung toxicity. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) is an adaptive radiation therapy regimen where radiation pulses are delivered over longer periods of time, thereby allowing for modification of the treatment based on the patient's response, as well as limiting toxicities. As such, we hypothesize that treating patients with poor pulmonary function using a PULSAR approach is better tolerated in when compared to patients treated with SAbR. We performed a retrospective review of our institutional database of patients treated with SAbR to lung lesions from 2005 to 2022. We assessed the overall survival in stage-matched patients with normal vs poor lung function who received SAbR (40 patients in each cohort). Patients with decreased lung function included those with a diagnosis of moderate/severe COPD, restrictive lung disease, or patients needing home oxygen at the time of treatment. We then analyzed PFTs changes for patients receiving SAbR, and evaluated these changes relative to treatment delivery. Stage-matched Kaplan-Meier analysis of patients with normal vs poor lung function receiving SAbR revealed a statistically significant difference in survival with Log-rank test p = 0.007. Of the patients with PFTs, 45 (90%) received SAbR with two to three treatments weekly, while 5 (10%) were treated on a PULSAR regimen with one fraction every week to three weeks. No trends or significant differences are observed in the changes of total lung capacity (TLC), the first second of exhalation (FEV1), forced vital capacity (FVC) or FEV1/FVC ratios. However, we did note variations in the diffusing capacity of the lung for carbon monoxide (DLCO). The mean difference in DLCO for the SAbR and PULSAR groups were -26.07% (95% CI: -31.28 to -20.87, p < 0.0001), and -10.52% (95% CI: -40.74 to 19.69, p = 0.388), respectively. We observed a significant difference in overall survival between patients with normal vs poor lung function receiving SAbR. In a preliminary analysis, we discovered a small decline in DLCO for patients treated with regularly scheduled SAbR treatments. In the patients treated on the PULSAR regimen, however, this change in DLCO is not statistically significant. While this data suggests that increasing the time frame between individual doses of radiation may result in better toleration of radiotherapy in this patient population, the sample size of patients treated via PULSAR is limited, and longer follow-up is needed to further evaluate the potential benefits.

An early Indian experience with benralizumab - A compendium on severe asthma cases: a case series.

Background: Severe eosinophilic asthma (SEA), one of the phenotypes of asthma that is characterized by elevated blood eosinophil counts, is a common cause of uncontrolled asthma. Patients with SEA often experience severe persistent symptoms and have frequent exacerbations despite optimal inhaler therapy. They also have poor lung function and quality of life (QoL). Benralizumab (Fasenra), a monoclonal antibody, has been approved for managing cases of SEA. This series of six cases, the first of its kind from India, aims to add to the real-world evidence of benralizumab in India. Methods: Benralizumab 30 mg (once in four weeks for the first three doses followed by a dose every eight weeks for two years) was administered in six patients with symptoms of cough, breathlessness on exertion, and wheezing, diagnosed with SEA. The following were the endpoints assessed: (i) overlap between high immunoglobulin E (IgE) and eosinophilic asthma; (ii) reduction of exacerbations; (iii) withdrawal of oral corticosteroids; and (iv) improvement in lung function and QoL. Results: In all cases, management with benralizumab resulted in optimal clinical and functional improvement, a decline in systemic steroid use, and improved QoL. Conclusions: The cases presented here are the first of their kind in the Indian asthmatic population with all SEA patients demonstrating significant improvement in symptoms with the use of benralizumab.

The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2–5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. MethodsA real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. ResultsA cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was −40.95 ± 438.26 mL and −0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). ConclusionsIn this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Prevalence and assessment of frailty in interstitial lung disease - a systematic review and meta-analysis.

Frailty is a multisystem dysregulation that challenges homeostasis and increases vulnerability towards stressors. In patients with interstitial lung diseases (ILD) frailty is associated with poorer lung function, greater physical impairment, and higher symptom burden. Our understanding of the prevalence of frailty in ILD and consequently its impact on the ILD population is limited. We aimed to systematically review frailty assessment tools and to determine frailty prevalence across different ILD cohorts. Meta-analyses were used to calculate the pooled prevalence of frailty in the ILD population. We identified 26 studies (15 full-texts, 11 conference abstracts) including a total of 4614 patients with ILD. The most commonly used frailty assessment tools were the Fried Frailty Phenotype (FFP), the Short Physical Performance Battery (SPPB), and the cumulative Frailty Index (FI). Data allowed for meta-analyses of FFP and SPPB prevalence. The pooled prevalence of frailty was 35% (95% CI 25%-45%) by FFP, and 19% (95% CI 12%-28%) by SPPB. Frailty is common in ILD, with considerable variability of frailty prevalence depending on the frailty assessment tool used. These findings highlight the importance of frailty in ILD and the need for a standardized approach to frailty assessment in this population.

Cost-effectiveness analysis of grass pollen specific immunotherapy in children with allergic rhinitis compared to the standard of care symptomatic treatment in Portugal.

Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.