Decline In Pulmonary Function Research Articles

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It is associated with cough, dyspnea and impaired quality of life. If left untreated, IPF has a median survival of 3 years.IPF affects ∼3 million people worldwide, with increasing incidence in older patients. The current concept of pathogenesis is that pulmonary fibrosis results from repetitive injury to the lung epithelium, with fibroblast accumulation, myofibroblast activation, and deposition of matrix. These injuries, in combination with innate and adaptive immune responses, dysregulated wound repair and fibroblast dysfunction, lead to recurring tissue remodeling and self-perpetuating fibrosis as seen in IPF.The diagnostic approach includes the exclusion of other interstitial lung diseases or underlying conditions and depends on a multidisciplinary team-based discussion combining radiological and clinical features and well as in some cases histology. In the last decade, considerable progress has been made in the understanding of IPF clinical management, with the availability of two drugs, pirfenidone and nintedanib, that decrease pulmonary lung function decline. However, current IPF therapies only slow disease progression and prognosis remains poor. Fortunately, there are multiple clinical trials ongoing with potential new therapies targeting different disease pathways.This review provides an overview of IPF epidemiology, current insights in pathophysiology, diagnostic and therapeutic management approaches. Finally, a detailed description of current and evolving therapeutic approaches is also provided.

Profiling Microbiota from Multiple Sites in the Respiratory Tract to Identify a Biomarker for PM2.5 Nitrate Exposure-Induced Pulmonary Damages.

The microbiota present in the respiratory tract (RT) responds to environmental stimuli and engages in a continuous interaction with the host immune system to maintain homeostasis. A total of 40 C57BL/6 mice were divided into four groups and exposed to varying concentrations of PM2.5 nitrate aerosol and clean air. After 10 weeks of exposure, assessments were conducted on the lung and airway microbiome, lung functions, and pulmonary inflammation. Additionally, we analyzed data from both mouse and human respiratory tract (RT) microbiomes to identify possible biomarkers for PM2.5 exposure-induced pulmonary damages. On average, 1.5 and 13.5% inter-individual microbiome variations in the lung and airway were explained by exposure, respectively. In the airway, among the 60 bacterial OTUs (operational taxonomic units) > 0.05% proportion, 40 OTUs were significantly affected by PM2.5 exposure (FDR ≤ 10%). Further, the airway microbiome was associated with peak expiratory flow (PEF) (p = 0.003), pulmonary neutrophil counts (p = 0.01), and alveolar 8-OHdG oxidative lesions (p = 0.0078). The Clostridiales order bacteria showed the strongest signals. For example, the o_Clostridiales;f_;g_ OTU was elevated by PM2.5 nitrate exposure (p = 4.98 × 10-5) and negatively correlated with PEF (r = -0.585 and p = 2.4 × 10-4). It was also associated with the higher pulmonary neutrophil count (p = 8.47 × 10-5) and oxidative lesion (p = 7.17 × 10-3). In human data, we confirmed the association of airway Clostridiales order bacteria with PM2.5 exposure and lung function. For the first time, this study characterizes the impact of PM2.5 exposure on the microbiome of multiple sites in the respiratory tract (RT) and its relevance to airflow obstructive diseases. By analyzing data from both humans and mice, we have identified bacteria belonging to the Clostridiales order as a promising biomarker for PM2.5 exposure-induced decline in pulmonary function and inflammation.

Risk factors for the deterioration of pulmonary function in primary ciliary dyskinesia.

PCD is a genetic disease leading to a decline in pulmonary function. There is only little knowledge of factors determining the long-term pulmonary outcome. Especially adherence has not been addressed yet although being an independent risk factor for an increased loss of lung capacity in other chronic respiratory diseases. Assessing the impact of bacterial airway colonization and adherence on long-term lung function in patients with PCD. Data on colonization and lung function parameters like forced expiratory volume in the first second (FEV1, Z-score) and lung clearance index (LCI2,5% ) were collected for 7.01 ± 2.2 years (893 quarters) in 44 PCD patients. Adherence was classified as good, moderate or poor. The impact of both adherence and colonization was assessed for the long-term course of FEV1, the association of colonization with lung function also quarterly. Kruskall-Wallis test, T test, ANOVA, linear regression, linear mixed model. Chronic colonization did not show any impact on the for long-term course of FEV1 , but adherence was a significant factor: patients with good adherence showed better FEV1 at the end of the observation period than children with poor adherence (-0.15 ± 0.88 vs. -2.63 ± 1.79, p < 0.01). Adherence has not yet been investigated for PCD. However, we found it to be a major significant factor affecting long-term FEV1 in PCD. Thus, it should be taken into consideration in the treatment protocols for PCD.

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience.

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment's efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was -0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline.

JAK-STAT activation contributes to cytotoxic T cell–mediated basal cell death in human chronic lung allograft dysfunction

Chronic lung allograft dysfunction (CLAD) is the leading cause of death in lung transplant recipients. CLAD is characterized clinically by a persistent decline in pulmonary function and histologically by the development of airway-centered fibrosis known as bronchiolitis obliterans. There are no approved therapies to treat CLAD, and the mechanisms underlying its development remain poorly understood. We performed single-cell RNA-Seq and spatial transcriptomic analysis of explanted tissues from human lung recipients with CLAD, and we performed independent validation studies to identify an important role of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling in airway epithelial cells that contributes to airway-specific alloimmune injury. Specifically, we established that activation of JAK-STAT signaling leads to upregulation of major histocompatibility complex 1 (MHC-I) in airway basal cells, an important airway epithelial progenitor population, which leads to cytotoxic T cell-mediated basal cell death. This study provides mechanistic insight into the cell-to-cell interactions driving airway-centric alloimmune injury in CLAD, suggesting a potentially novel therapeutic strategy for CLAD prevention or treatment.

Cesium exposure and pulmonary function decline: Potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients

Cesium (Cs) is one of alkali metals. Persistent low-dose Cs exposure damages pulmonary function in the general population. However, the associations between Cs exposure and pulmonary function alternation are inconsistent in chronic obstructive pulmonary disease (COPD) patients. Thus, the goal of this study was to estimate the association between blood Cs concentration and pulmonary function alternation and the potential role of oxidative stress in this association. Serum 8-iso-prostaglandin F2α (8-iso-PGF2α) and blood Cs were measured. A generalized additive model and smoothed curve fitting found a non-linear relationship between blood Cs concentration and pulmonary function in COPD patients. Under the inflection point of blood Cs, per 1-unit increase of blood Cs was related with reductions of 0.592 L (95% CI: −1.181, −0.004) in FVC and 32.479% (95% CI: −55.278, −9.680) in predicted FEV1% with adjustment for confounding variables. Smoking status aggravated Cs-caused pulmonary function reduction in COPD patients. Sensitivity analyses hinted that our results remained robust. Moreover, a negatively linear correlation (β = 0.232; 95% CI: 0.105, 0.359) between blood Cs within a certain range and serum 8-iso-PGF2α was observed. Further investigation elucidated serum 8-iso-PGF2α was inversely correlated with pulmonary function parameters in COPD patients. Additionally, mediation analysis suggested that 8-iso-PGF2α mediated 6.70% and 8.36% of the associations between blood Cs with the reductions of FEV1 and predicted FEV1%, respectively. Consequently, blood Cs was inversely associated with pulmonary function parameters, but positively related with serum 8-iso-PGF2α. Oxidative stress may exert an important role in mediating Cs exposure-associated pulmonary function reduction in COPD patients.

Abstract P194: Proteomic Profiling of Pulmonary Function Decline and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Measures of pulmonary function are associated with cardiovascular disease risk; however, the underlying mechanism remains unclear. Hypothesis: We hypothesize that protein biomarkers are associated with pulmonary function decline, as well as the risk of subsequent incident coronary heart disease (CHD), heart failure (HF), and mortality. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study with plasma proteome measured by SOMAscan and spirometric measures (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC)) at both visits 2 (1990-1992) and 5 (2011-2013). Cross-sectional associations of protein levels with FEV1 and FVC at both visits were assessed using multivariable linear regression. The decline of FEV1 was evaluated among proteins related to cross-sectional FEV1 and FVC measures. The FEV1-decline-related proteins were further probed into the effects on incident CHD, HF, and mortality, using Cox proportional hazard models post-visit 2. Results: Out of 4,677 proteins, 364 were cross-sectionally associated with both FEV1 and FVC at visit 2 (n=11,354, age 57, 23% blacks, and 56% women) and 5 (n=3,517, age 75, 17% blacks, and 58% women) at FDR &lt;0.05. Twenty-seven of 364 proteins were associated with FEV1 decline between visits (FDR &lt;0.05). The protein effects were more predominant in women than men (p &lt;0.001). Among 27 FEV1 decline-related proteins, 25 and 27 were associated with incident HF and mortality during an average of 29 years follow-up (FDR &lt;0.05, Figure ). Gamma-aminobutyric acid receptor-associated protein showed the greatest effect with FEV1 decline, and its per SD increase was associated with 20% higher risk of HF and mortality. Compared to HF and mortality, FEV1 decline-related proteins were less associated with incident CHD. Conclusions: Twenty-seven proteins related to pulmonary function decline were heavily associated with the risk of HF and mortality, suggesting shared etiology between those conditions.

Serum lactate dehydrogenase is associated with impaired lung function: NHANES 2011-2012.

Serum lactate dehydrogenase levels reflect disease status in a variety of organs, but its role in indicating pulmonary function is not yet clear. Therefore, this study explored the correlation between pulmonary function and serum lactate dehydrogenase, and investigated thresholds for changes in pulmonary function indicators in the total population as well as in different strata of the population. Based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 (n = 3453), univariate and stratified analyses were performed to investigate factors associated with pulmonary function, and multiple regression analysis was used to further investigate the specific relationship with serum lactate dehydrogenase. Smoothed curve fitting, threshold effect and saturation effect analysis were used to explore the threshold level of serum lactate dehydrogenase at the onset of changes in pulmonary function indicators. Adjusted smoothed curve fit plots showed a linear relationship between serum lactate dehydrogenase levels and forced vital capacity and forced expiratory volume in one second: for each 1 U/L increase in serum lactate dehydrogenase levels, forced vital capacity decreased by 1.24 mL (95% CI = -2.05, -0.42, P = 0.0030) and forced expiratory volume in one second by 1.11 mL (95% CI = -1.82, -0.39, P = 0.0025). Serum lactate dehydrogenase was negatively and linearly correlated with pulmonary function indices in the total population analyzed. Based on the total population and different population stratifications, this study determined the threshold values of serum lactate dehydrogenase at the onset of decline of pulmonary function in different populations. This provides a new serological monitoring indicator for patients suffering from respiratory diseases and has implications for patients with possible clinical impairment of pulmonary function. However, our cross-sectional study was not able to determine a causal relationship between these two factors, and further research is needed.

Increased Exacerbation Burden in Allergic Polysensitized Patients with Moderate to Severe Asthma

Using a machine learning algorithm, we recently reported allergic poly-sensitization (APS) clusters based on ImmunoCAP® results as a newly recognized severity marker in adult urban asthmatics. APS clusters, based on numbers of positive allergen sensitizations and allergen-specific IgE levels can predict pulmonary function decline, total IgE levels and eosinophilia. Also, we found “superclusters” (cluster groupings) that tracked patients with either predominately seasonal or perennial allergen sensitizations.

Hesperidin inhibits lung fibroblast senescence via IL-6/STAT3 signaling pathway to suppress pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease with obscure pathogenesis. Increasing evidence suggests that cellular senescence is an important mechanism underlying in IPF. Clinical treatment with drugs, such as pirfenidone and nintedanib, reduces the risk of acute exacerbation and delays the decline of pulmonary function in patients with mild to moderate pulmonary fibrosis, and with adverse reactions. Hesperidin was previously shown to alleviate pulmonary fibrosis in rats by attenuating the inflammation response. Our previous research indicated that the Citrus alkaline extracts, hesperidin as the main active ingredient, could exert anti-pulmonary fibrosis effects by inhibiting the senescence of lung fibroblasts. However, whether hesperidin could ameliorate pulmonary fibrosis by inhibiting fibroblast senescence needed further study. PurposeThis work aimed to investigate whether and how hesperidin can inhibit lung fibroblast senescence and thereby alleviate pulmonary fibrosis MethodsBleomycin was used to establish a mouse model of pulmonary fibrosis and doxorubicin was used to establish a model of cellular senescence in MRC-5 cells in vitro. The therapeutic effects of hesperidin on pulmonary fibrosis using haematoxylin-eosin staining, Masson staining, enzyme-linked immunosorbent assay, immunohistochemistry, western blotting and quantitative Real-Time PCR. The anti-senescent effect of hesperidin in vivo and in vitro was assessed by western blotting, quantitative Real-Time PCR and senescence-associated β‐galactosidase ResultsWe demonstrated that hesperidin could alleviate bleomycin-induced pulmonary fibrosis in mice. The expression level of senescence marker proteins p53, p21, and p16 was were downregulated, along with the myofibroblast marker α-SMA. The number of senescence-associated β-galactosidase-positive cells was significantly reduced by hesperidin intervention in vivo and in vitro. In addition, hesperidin could inhibit the IL6/STAT3 signaling pathway. Furthermore, suppression of the IL-6/STAT3 signaling pathway by pretreatment with the IL-6 inhibitor LMT-28 attenuating effect of hesperidin on fibroblast senescence in vitro. ConclusionsThese data illustrated that hesperidin may be potentially used in the treatment of IPF based on its ability to inhibit lung fibroblast senescence.

Association between cadmium exposure and pulmonary function reduction: Potential mediating role of telomere attrition in chronic obstructive pulmonary disease patients

BackgroundEnvironmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. MethodsAll eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). ResultsBlood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. ConclusionBlood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

Clinical outcomes of dose modification during pirfenidone treatment for IPF: A nationwide post-marketing surveillance study.

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800mg, 1,200mg, and <1,200mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy.

Impact of Previous Pulmonary Tuberculosis on Chronic Obstructive Pulmonary Disease: Baseline Results from a Prospective Cohort Study.

Pulmonary tuberculosis (PTB) is a significant risk factor for COPD, and Xinjiang, China, has a high incidence of pulmonary tuberculosis. The effects of tuberculosis history on airflow restriction, clinical symptoms, and acute episodes in COPD patients have not been reported in the local population. Besides, the exact relationship between lung function changes in people with a history of tuberculosis and COPD risk is not clear. This study is based on the Xinjiang baseline survey data included in the Natural Population Cohort Study in Northwest China from June to December, 2018. Subjects' questionnaires, physical examination, and lung function tests were performed through a face-to-face field survey to analyze the impact of previous pulmonary tuberculosis on local COPD. Furthermore, we clarified the specific relationship between pulmonary function decline and the probability of developing COPD in people with a history of tuberculosis. A total of 3249 subjects were eventually enrolled in this study, including 87 with a history of tuberculosis and 3162 non-TB. The prevalence of COPD in the prior TB group was significantly higher than that in the control group (p-value = 0.005). First, previous pulmonary tuberculosis is an essential contributor to airflow limitation in the general population and patients with COPD. In all subjects included, pulmonary function, FEV1% predicted (p-value < 0.001), and FEV1/FVC (%) (p-value < 0.001) were significantly lower in the prior TB group than in the control group. Compared to non-TB group, FEV1% prediction (p-value = 0.019) and FEV1/FVC (%) (p-value = 0.016) were found to be significantly reduced, and airflow restriction (p-value = 0.004) was more severe in prior TB group among COPD patients. Second, COPD patients in the prior TB group had more severe clinical symptoms. Compared with no history of tuberculosis, mMRC (p-value = 0.001) and CAT (p-value = 0.002) scores were higher in the group with a history of tuberculosis among COPD patients. Third, compared with the non-TB group, the number of acute exacerbations per year (p-values=0.008), the duration of each acute exacerbation (p-values=0.004), and hospitalization/ patient/year (p-values<0.001) were higher in the group with a history of tuberculosis among COPD patients. Finally, a dose-response relationship between FEV1/FVC (%) and the probability of developing COPD in people with previous pulmonary TB was observed; when FEV1/FVC (%) was < 80.8, the risk of COPD increased by 13.5% per unit decrease in lung function [0.865(0.805, 0.930)]. COPD patients with previous pulmonary tuberculosis have more severe airflow limitations and clinical symptoms and are at higher risk for acute exacerbations. Furthermore, lung function changes in people with a history of tuberculosis were associated with a dose-response relationship with the probability of developing COPD.

Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease.

Eosinophils are important effector cells in airway inflammation, as pleiotropy and heterogeneity can be linked to various pathophysiologies in asthma and chronic obstructive pulmonary disease (COPD). Sputum eosinophils can reflect the heterogeneity of airway inflammation, and owing to their traits, blood eosinophils can be a surrogate and potential biomarker for managing both conditions. Blood eosinophils are activated via the stimulation of type 2 cytokines, such as interleukin (IL)-5, IL-4/13, granulocyte-macrophage colony-stimulating factor, IL-33, and thymic stromal lymphopoietin. There is sufficient evidence to support the relationship between the blood eosinophil count and clinical outcomes, including pulmonary function decline, exacerbations, all-cause mortality, and treatment response to inhaled corticosteroids and biologics. Thus, there is growing interest in the use of blood eosinophils for the management of these diseases. Compiling recent evidence, we herein review the significance of measuring blood eosinophils in asthma and COPD.

The Prevalence of Diabetes Mellitus Type 2 in Severe and Very Severe Chronic Obstructive Pulmonary Disease Patients

Background: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There is evidence to support a connection between COPD and Diabetes mellitus type 2 (T2DM). T2DM affects 2-37% of COPD patients, with results being highly variable between studies. Objective :To determine the prevalence of T2DM in patients with severe and very severe stages of COPD and to assess the risk factors affecting the prevalence of T2DM among COPD patients. Methods: A cross sectional study was conducted on 140 patients with COPD attending Outpatient and Inpatient of Respiratory Unit at Baghdad Teaching Hospital. The data were collected between the 10th of October 2016 to the 10th of August 2017. These data included demographic parameters such as: age, sex, smoking habit, and respiratory parameters from history and clinical examination. Spirometry was used to assess the severity of COPD patients. Random blood sugar testing was used for identification of COPD patients having T2DM when they are not clear or not known as a case of T2DM previously. Results: The prevalence of T2DM among COPD patients was 19.38%; the prevalence of T2DM in those with severe stage was 10.9%, while in very severe stage was 35.4%. In comparison to women, men were more likely to have T2DM.The prevalence of T2DM increased in the elderly COPD patients (&gt;61 years), with high body mass index, and also increased more among current smokers followed by former smokers and never smokers. Lung function tests decline more in COPD patients with presence of T2DM. Conclusion: T2DM is more common among COPD patients, and its prevalence rose as the severity of the COPD patients' condition worsened. Additionally, T2DM patients are more likely to experience a decline in pulmonary function. Keywords: Diabetes mellitus type 2, chronic obstructive pulmonary disease, prevalence, random blood sugar Citation: Al-Ani NAH, Al-Obaidy MW. The prevalence of diabetes mellitus type 2 in severe and very severe chronic obstructive pulmonary disease patients. Iraqi JMS. 2022; 20(2): 269-277. doi: 10.22578/IJMS.20.2.15

Risk factors for long-term decline in post-operative pulmonary function after lung resection.

The study aimed to examine the risk factors for long-term decline in pulmonary function after anatomical resection for lung cancer and the effects of the decrease on survival. We retrospectively examined 489 patients who underwent anatomical resection for lung cancer between 2010 and 2020. Pulmonary function tests were performed preoperatively and at 1, 3, 6 and 12months after surgery. The lower interquartile medians of the reduction rates of forced expiratory volume in 1s and vital capacity at 12months after surgery were taken as the cut-off values of risk factors for the decrease in post-operative pulmonary function. Forced expiratory volume in 1s and vital capacity decreased the most in the first month after surgery and then gradually recovered. Vital capacity continued to increase even after 6months post-surgery, whereas forced expiratory volume in 1s stabilized. Multivariable logistic analysis showed that the number of resected segments (odds ratio, 2.09; 95% confidence interval, 1.12-3.89; P=0.019) was a risk factor for the decrease in forced expiratory volume in 1s at 12months, and the numbers of resected segments (odds ratio, 1.36; 95% confidence interval, 1.13-1.63; P<0.001) and post-operative complications (odds ratio, 2.32; 95% confidence interval, 1.01-5.35; P=0.047) were independent risk factors for decrease in vital capacity. Multivariate cox regression analysis showed that the decrease in vital capacity at 12months was significantly associated with overall survival (hazard ratio, 2.02; 95% confidence interval, 1.24-3.67; P=0.004). Long-term decrease in vital capacity, which was influenced by the number of resected segments and post-operative complications, adversely affected survival.

Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer.

The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy. Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r). Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively). The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.

Lung Transplantation for COVID-19 Acute Respiratory Distress Syndrome: The British Columbian Experience With New Disease Pathology

Lung transplantation is a life-saving treatment for patients with end-stage lung disease. COVID-19 has been associated with a severe and rapid decline in pulmonary function, in which case lung transplantation has been described to be effective. We herein describe 9 patients who underwent lung transplantation for COVID-19 acute respiratory distress syndrome, of whom 6 were bridged with extracorporeal membrane oxygenation (ECMO). The median time of pre-operative observation periods was 54 days to ensure no lung function recovery and the time to wean off extracorporeal membrane oxygenation was 3 days. Patients had comparable short-term survival outcomes to non-COVID-19 lung transplant recipients at our institution during the same time period. Lung transplantation for COVID-19-associated lung disease is feasible with comparable short-term outcomes and may liberate patients from extracorporeal supports.

Immunomodulatory treatment in unclassifiable interstitial lung disease: A retrospective study of treatment response.

The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients. Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities. Sixty-five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was -0.22%, [-0.34; -0.11], and -0.15% [-0.28;-0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, -0.082% per month, [-0.28; 0.11], p= 0.10 for FVC and -0.14% per month, [-0.36; 0.079], p= 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p= 0.12, and for DLco, 0.0085% per month, p= 0.7. The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management.

Physical Activity and Quality of Life among Patients with Cystic Fibrosis.

Physical activity (PA) improves exercise capacity, slows the decline in lung function, and enhances Quality of Life (QoL) in patients with cystic fibrosis (pwCF). The study aimed to evaluate PA and QoL among children with CF compared to healthy controls; the secondary aim was to assess the correlation between PA, QoL, and lung function (FEV1). Forty-five children and adolescents with CF and 45 age-matched controls completed two self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the DISABKIDS for QoL. Moreover, pwCF performed spirometry and multiple breath washout tests (MBW). In addition, weight, height, and BMI were recorded. The Godin Leisure-Time Exercise Questionnaire was used to evaluate physical activity; QOL was assessed using the DISABKIDS Questionnaire. The correlation of PA with QOL was assessed as well. Mean age of the CF population was 13.22 (±4.6) years, mean BMI 19.58 (±4.1) kg/m2, mean FEV1% 91.15 ± 20.46%, and mean LCI 10.68 ± 4.08. 68% of the CF group were active, 27% were medium active, 5% were sedentary, while 83% of the control group were active and 17% were medium active. PwCF with higher PA scores showed significantly higher emotional health (r2: 0.414, p: 0.006) and total QOL score (r2: 0.372; p: 0.014). The PA score showed no significant correlation with FEV1% or LCI. The children with CF showed satisfactory PA levels, which positively correlated to their QoL. More research is needed on the effect of increased levels of habitual physical activity to establish the decline in pulmonary function among pwCF.