Decrease In FEV1 Research Articles

The relationship between pulmonary ventilation function and bone marrow hematopoietic function: A mendelian randomization analysis

Background: In recent years, the comorbidity between respiratory and hematopoietic system diseases has emerged as a new challenge. However, the potential genetic link between the ventilatory function of the respiratory system and the hematopoietic function of the bone marrow remains unclear. In this study, we conducted a comprehensive investigation into the possible genetic connection between lung ventilatory function and bone marrow hematopoietic function. Methods: We selected two exposure factors, Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC), which represent pulmonary ventilation function, and two outcome indicators, Immature Fraction of Reticulocytes (IFR) and Reticulocyte Count (RC), which represent bone marrow hematopoiesis function, from published genome-wide association studies. Based on the three core assumptions of Mendelian randomization analysis, we extracted Single Nucleotide Polymorphism (SNPs) associated with FEV1 and FVC as instrumental variables for the exposure factors. We then conducted two-sample Mendelian randomization analyses using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. Lastly, we assessed the reliability of the testing results through MR-Egger, Cochran’s Q test, and the leave-one-out test. Through these steps, we aimed to explore the causal relationship between pulmonary ventilation function and the outcome of bone marrow hematopoiesis function and evaluated the reliability of the testing results using methods such as MR-Egger, Cochran’s Q test, and the leave-one-out test. Results: The IVW method revealed that a decrease in FEV1 is associated with an increase in IFR (β = −0.072, 95% CI: −0.131 to −0.014, p = 0.01), and the results from MR-Egger regression showed a similar association (β = −0.169, 95% CI: −0.342 to −0.004, p = 0.05). Furthermore, a decrease in FEV1 is associated with an increase in RC (β = −0.143, 95% CI: −0.198 to −0.087, p =4.00E-07), and MR-Egger regression yielded consistent results (β = −0.216, 95% CI: −0.381 to −0.541, p=1.07E-02). Similarly, a decrease in FVC is associated with an increase in IFR (β = −0.073, 95% CI: −0.116 to −0.031, p = 6.17E-04), and MR-Egger regression showed a similar trend (β = −0.046, 95% CI: −0.160 to −0.067, p=0.42). Additionally, a decrease in FVC is associated with an increase in RC (β = −0.173, 95% CI: −0.221 to −0.125, p = 2.33E-12), and MR-Egger regression yielded consistent results (β = −0.142, 95% CI: −0.272 to −0.012, p = 3.32E-02). The reliability tests indicated heterogeneity in the above MR analyses but no evidence of horizontal pleiotropy. Therefore, a fixed-effect model IVW was used to explore the causal relationships, which were found to be robust and reliable with no outliers or significant bias in this study. Conclusion: This study indicates that there is a negative causal relationship between pulmonary ventilation function and bone marrow hematopoietic function. A decrease in pulmonary ventilation function stimulates bone marrow hematopoiesis. However, further research is needed to elucidate this mechanism.

A phase 2 multicenter trial of ruxolitinib to treat bronchiolitis obliterans syndrome after allogeneic HCT

AbstractBronchiolitis obliterans syndrome (BOS) occurring after allogeneic hematopoietic cell transplantation (HCT) is a high-risk manifestation of chronic graft-versus-host disease. In this prospective, multicenter phase 2 trial, adult participants with BOS were treated with ruxolitinib 10 mg twice daily, continuously in 28-day cycles for up to 12 cycles. Participants enrolled into newly diagnosed (<6 months since BOS diagnosis, cohort A) or established (≥6 months since BOS diagnosis, cohort B) disease cohorts. The primary objective was to evaluate the early treatment effect of ruxolitinib, assessed by the change in forced expiratory volume in 1 second (FEV1) at 3 months compared with enrollment. The primary end point differed according to cohort (cohort A, improvement, defined as ≥10% increase in FEV1; cohort B, stabilization, defined as an absence of ≥10% decrease in FEV1). Between 2019 and 2022, 49 participants meeting the criteria for BOS were enrolled and treated (cohort A, n = 36; cohort B, n = 13). The primary end point was achieved by 27.8% of participants with new BOS and 92.3% of participants with established BOS. According to the 2014 National Institutes of Health Consensus Criteria, the best lung-specific overall response rate on ruxoltinib for the 49 participants was 34.7% (16.3% complete response and 18.4% partial response), with most responses occurring in mild or moderate disease. Noninfectious severe (grade ≥3) treatment-emergent adverse events were infrequent. Nine severe infectious events occurred and were largely respiratory in nature. These results support the use of ruxolitinib in the management of BOS after allogeneic HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03674047.

(FEV3-FEV1)/FVC: A Terminal-Airflow Variable for Airway Hyperresponsiveness and Inflammation Prediction in Patients With Symptoms Despite Preserved Spirometry

BackgroundSmall-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention. ObjectiveThis study investigated whether the ratio of forced expiratory volume in the second and third seconds to forced vital capacity ([FEV3-FEV1]/FVC) correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry. MethodsThis cross-sectional study enrolled patients with FEV1 ≥ 80% predicted, FEV1/FVC ≥ 0.7, and recurring asthma-like symptoms. Data included demographics, fractional exhaled nitric oxide (FeNO), impulse oscillometry, and spirometry. Univariate and combined models predicting AHR was analyzed in 553 patients and validated in 561. Correlations between sputum inflammation and spirometrics were also assessed. ResultsAHR+ patients exhibited higher (FEV3-FEV1)/FVC ratios compared to AHR-. This ratio showed the strongest association with the methacholine dose causing a 20% FEV1 decrease (PD20) and the response dose ratio (RDR)(r = -0.26 and 0.39, respectively; P < .001, both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV3-FEV1)/FVC was 0.751, increasing to 0.821 when combined with FeNO, confirmed in the validation cohort. (FEV3-FEV1)/FVC was superior to maximal expiratory flow at 50% of forced vital capacity for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics. ConclusionElevated (FEV3-FEV1)/FVC were evident in AHR+ patients with preserved FEV1/FVC ratios. It serves as a sensitive marker of AHR and airway inflammation correlating with RDR, PD20, and sputum eosinophils, suggesting its utility in monitoring patients at risk for uncontrolled asthma.

Lung function decline in people with serious mental illness: A call to action

This prospective observational study aimed to evaluate the rate of change in forced expiratory volume in the first second (FEV1) and to explore the factors associated with changes in FEV1 in people with serious mental illness (SMI). Sixty subjects diagnosed with schizophrenia or bipolar disorder who were smokers and without history of respiratory illness agreed to participate. The mean (range) follow-up period was 3.54 (3.00–4.98) years. The mean (standard deviation) annual rate of change in FEV1 decreased by 39.1 (105.2) mL/year. Thirty-one (51.7 %) patients experienced a decrease in the FEV1 ≥40 mL/year (i.e. a rapid decline). The factors associated with the absolute change in FEV1 were the baseline International Physical Activity Questionnaire activity score in metabolic equivalents of tasks (β 0.145, 95 % confidence interval [CI] 0.043 to 0.246; p = 0.005), baseline FEV1 (β -0.025, 95 % CI -0.076 to 0.027; p = 0.352), and the interaction term of both variables (β -3.172e-05, 95 % CI -6.025e-05 to -0.319e-05; p = 0.029). The factors associated with rapid FEV1 decline were income (odds ratio [OR] 0.999, 95 % CI 0.995 to 1.003; p = 0.572), the rate of change in abdominal circumference (OR 0.000, 95 % CI 0.000 to 0.890; p = 0.081), and the interaction term of both variables (OR 1.038, 95 % CI 1.010 to 1.082; p = 0.026). In conclusion, a substantial proportion of people with SMI experienced a rapid decrease in FEV1. If our results are confirmed in larger samples, the routine evaluation of lung function in people with SMI would be an opportunity to identify individuals at greater risk of morbidity and mortality.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients

BackgroundExposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown.MethodsThe cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models.ResultsEach 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively.ConclusionBlood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Effects of oscillatory positive expiratory pressure therapy in patients undergoing thoracic or upper abdominal surgery: A systematic review and meta-analysis

BackgroundPreventing postoperative complications and accelerating patient recovery are critical issues in clinical treatment and nursing care. This meta-analysis aimed to evaluate the effects of oscillatory positive expiratory pressure therapy (OPEPT) in patients undergoing thoracic or abdominal surgery. MethodsWe searched PubMed, the Cochrane Library, Web of Science, EBSCO, SinoMed, Weipu, WanFang, and China National Knowledge Infrastructure (CNKI) for randomized controlled trials (RCTs) on the role of OPEPT on patients undergoing thoracic and upper abdominal surgeries. Two researchers independently conducted literature screening, quality assessment, and data extraction based on the inclusion and exclusion criteria, and used the RevMan 5.4 software to perform the meta-analysis. ResultsA total of 13 RCTs involving 1166 patients undergoing thoracic or abdominal surgery were included. The meta-analysis results showed that the decreases in FEV1[MD = 0.30, 95%CI (0.22, 0.38), P < 0.001] and FVC levels [MD = 0.38, 95%CI (0.26, 0.49), P < 0.001] were statistically less in the OPEPT group than those in the control group. OPEPT could increase the postoperative drainage volume [MD = 91.53, 95%CI (57.55, 125.50), P < 0.001] and reduce the length of hospital stay [MD = −1.85, 95%CI (−3.42, −0.28), P = 0.02]. no significant effects on the FEV1/FVC [MD = 2.60, 95%CI (−0.46, 5.67), P = 0.10] and the indwelling time of drainage tube [MD = −1.39, 95%CI (−3.18, 0.41), P = 0.13] between patients undergoing OPEPT and routine care. No publication bias was detected amongst the synthesized outcomes (all P > 0.05). ConclusionOPEPT, with its promising therapeutic approach, has shown to positively influence the recovery process for patients undergoing thoracic and upper abdominal surgeries. More high-quality, large-sample studies are needed in the future to explore the efficacy and safety of OPEPT.

The Abbreviated Methacholine Challenge Test is Safe for Children

To evaluate the safety of an abbreviated methacholine challenge test (MCT) protocol in children. This prospective, observational study enrolled children aged 6 through 18 years referred for the MCT. The abbreviated protocol was initiated with a methacholine dose of 0.03 mg/ml and escalated in fourfold increments, unless the forced expiratory volume at 1 second (FEV1) decline exceeded 10%, at which point the next dose was only doubled. The safety of this abbreviated approach was assessed by monitoring adverse events, and specifically, decreases in FEV1 over 40%, hypoxemia, or uncontrollable cough. The number of methacholine doses and test duration were recorded and compared with estimated outcomes derived from the full-length MCT protocol. One hundred and twelve participants, aged 13.7 years (±3.3), successfully completed the protocol. Fifty-seven (51%) presented a positive MCT response. No significant clinical adverse events were observed. Of all participants, 2.7% exhibited an exaggerated response, in line with previously reported findings for the full-length protocol. The abbreviated approach resulted in an estimated average time-savings of 18:19 minutes per participant, thus reducing test length by 22:47 minutes for a negative MCT and by 14:34 minutes for a positive outcome. This abbreviated MCT protocol is safe for children and effectively shortens the duration of the MCT.

Unveiling the Respiratory Muscle Strength in Duchenne Muscular Dystrophy: The Impact of Nutrition and Thoracic Deformities, Beyond Spirometry.

Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, the predictability of upright-supine spirometry in terms of diaphragm involvement, and the impact of nutrition on muscle strength. This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. The effects of the ambulatory status, kyphoscoliosis, chest deformity, and low BMI on respiratory parameters were investigated. Forty-four patients were included in the study. The mean patient age was 10.8 ± 2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and non-ambulatory patients (p < 0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with a low BMI than in those without (p < 0.05). To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for nutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

Impact of Postoperative Prolonged Air Leakage on Long-Term Pulmonary Function after Lobectomy for Lung Cancer.

This study aimed to evaluate the long-term impact of postoperative prolonged air leak (PAL) on pulmonary function. We enrolled 1,316 patients with pathologic stage I-III lung cancer who underwent lobectomy. The cohort was divided into 2 groups: those who experienced PAL (n=55) and those who did not (n=1,261). Propensity score matching was conducted at a 1:4 ratio, resulting in 49 patients in the PAL group and 189 in the non-PAL group. Changes in pulmonary function were compared among preoperative, 6-month postoperative, and 12-month postoperative measurements between the 2 groups. The variables used for propensity score matching included age, sex, smoking history, body mass index, baseline pulmonary function, pathologic stage, and surgical approach. All standardized mean differences were less than 0.1. Six months postoperatively, the PAL group showed a greater reduction in both forced expiratory volume in 1 second (FEV1) (-13.0% vs. -10.0%, p=0.041) and forced vital capacity (FVC) (-15.0% vs. -9.0%, p<0.001) than the non-PAL group. In cases of upper lobectomy, there were no significant differences in FEV1 changes between the PAL and non-PAL groups at both 6 and 12 months. However, in lower lobectomy, the PAL group demonstrated a more pronounced decrease in FEV1 (-14.0% vs. -11.0%, p=0.057) and FVC (-20.0% vs. -13.0%, p=0.006) than the non-PAL group at 6 months postoperatively. Postoperative PAL delayed the recovery of pulmonary function after lobectomy. These effects were markedly more pronounced after lower lobectomy than after upper lobectomy.

Preoperative forced expiratory volume in one second and postoperative respiratory outcomes in nonpulmonary and noncardiac surgery: a retrospective cohort study

BackgroundAlthough the usefulness of pulmonary function tests has been established for lung resection and coronary artery bypass surgeries, the association between preoperative pulmonary function test and postoperative respiratory complications in nonpulmonary and noncardiac surgery is inconclusive. The purpose of this study was to determine the association between preoperative forced expiratory volume in one second (FEV1) on pulmonary function test and the development of postoperative respiratory failure and/or death in patients undergoing major nonpulmonary and noncardiac surgery.MethodsAdult patients aged ≥ 18 years and who underwent nonpulmonary and noncardiac surgery with expected moderate to high risk of perioperative complications from June 2012 to March 2019 were included. The primary exposure was preoperative FEV1 measured by pulmonary function test within six months before surgery. The primary outcome was respiratory failure (i.e., invasive positive pressure ventilation for at least 24 h after surgery or reintubation) and/or death within 30 days after surgery. A logistic regression model was used to adjust for the respiratory failure risk index, which is a scoring system that predicts the probability of postoperative respiratory failure based on patient and surgical factors, and to examine the association between preoperative FEV1 and the development of postoperative respiratory failure and/or death.ResultsRespiratory failure and/or death occurred within 30 days after surgery in 52 (0.9%) of 5562 participants. The incidence of respiratory failure and/or death in patients with FEV1 ≥ 80%, 70%– < 80%, 60%– < 70%, and < 60% was 0.9%, 0.6%, 1.7%, and 1.2%, respectively. Multivariable logistic regression analysis showed no significant association between preoperative FEV1 and postoperative respiratory failure and/or death (adjusted odds ratio per 10% decrease in FEV1: 1.01, 95% confidence interval: 0.88–1.17, P = 0.838). Addition of FEV1 information to the respiratory failure risk index did not improve the prediction of respiratory failure and/or death [area under the receiver operating characteristics curve: 0.78 (95% confidence interval: 0.72–0.84) and 0.78 (95% confidence interval: 0.72–0.84), respectively; P = 0.84].ConclusionWe found no association between preoperative FEV1 and postoperative respiratory failure and/or death in patients undergoing major nonpulmonary and noncardiac surgery.

Relation of changes in peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) during bronchoconstriction.

Diagnosis of asthma can be confirmed based on variability in peak expiratory flow (PEF) or changes in forced expiratory volume in 1 s(FEV1) measured with spirometry. Our aim was to use methacholine challenge as a model of induced airway obstruction to assess how well relative changes in PEF reflect airway obstruction in comparison to relative changes in FEV1. We retrospectively studied 878 patients who completed a methacholine challenge test. To assess congruency along with differences between relative changes in FEV1 and PEF during airway obstruction, a regression analysis was performed, and a Bland & Altman plot was constructed. ROC analysis, sensitivity, specificity, positive and negative predictive values and κ-coefficient were used to analyze how decrease in PEF predicts decrease of 10% or 15% in FEV1. The relative change in PEF was on average less than the relative change in FEV1. In the ROC analysis areas under the curve were 0.844 and 0.893 for PEF decrease to predict a 10% and 15% decrease in FEV1, respectively. The agreement between changes in PEF and FEV1 varied from fair to moderate. Airway obstruction detected by change in PEF was false in about 40% of cases when compared to change in FEV1. Change in PEF is not a very accurate measure of airway obstruction when compared to change in FEV1. Replacing peak flow metre with a handheld spirometer might improve diagnostic accuracy of home monitoring in asthma.

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

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

Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID

PurposeThe purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. MethodsThis study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant. ResultsThe Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 109/L vs. 3.43 ± 1.74 × 109/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014). ConclusionsThis study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.

Reversibility of bronchial obstruction in patients with primary ciliary dyskinesia to justify correction of inhalation therapy

Purpose. To assess the reversibility of bronchial obstruction in patients with primary ciliary dyskinesia in groups with and without concomitant allergic inflammation, with the aim of a differentiated approach to inhalation therapy and the validity of prescribing bronchodilators.Material and methods. Retrospective analysis of the results of FEV1 before and after inhalation of a bronchodilator and study of the dependence of the reversibility of obstruction on the presence of atopy markers.Results. Of 100 patients, 63% (n=63) had atopy markers; 37% (n=37) did not have these markers (p≤0.05). When comparing the FEV1 indicator in children with the presence of allergic burden (n=63) and in the absence of it (n=37), it was found that in patients with markers of atopy, obstructive changes identified during spirometry were 14.2% more common ( p≤0.05). Reversibility of bronchial obstruction was recorded in 24% (n=24), of which 87.5% (n=21) of patients had markers of atopy (p≤0.05). In children with concomitant allergic burden and a decrease in FEV1, reversibility of obstruction was detected in 48.4% (n=15) of cases (p≤0.05). It was revealed that in patients with the presence of atopy markers and a decrease in FEV1≤80%, reversibility of obstruction occurs 42.8% more often compared to the group of patients with a normal level of FEV1 (p≤0.05).Conclusions. The vast majority of patients with primary ciliary dyskinesia (n=63) have markers of atopy, mainly due to an isolated increase in total IgE in the blood serum (p≤0.05). A decrease in FEV1≤80% in children with allergies was detected 14.2% more often compared to the group of children without it (p≤0.05). In the vast majority of patients with an allergic phenotype, reversibility of obstruction was observed after a test with a bronchodilator. Thus, all patients with primary ciliary dyskinesia and the presence of atopy markers are recommended to undergo a test with a bronchodilator, and if reversibility of obstruction is detected, it is advisable to add a bronchodilator drug to therapy.

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.

CT trachea surface roughness is associated with chronic obstructive pulmonary disease symptoms

Abstract Background Trachea structural abnormalities occur in patients with chronic obstructive pulmonary disease (COPD), yet there are few methods for quantifying trachea surface topology. Purpose To develop a method to quantify trachea surface roughness on CT imaging and investigate the association with airflow limitation and symptoms in COPD. Materials and Methods Participants from the multicenter prospective Canadian Cohort Obstructive Lung Disease study between 2009 and 2015 underwent CT imaging and analysis. Established CT measurements included: tracheal index (TI), defined as the smallest ratio of coronal-to-sagittal trachea diameter, low attenuation areas below –950 HU, and wall thickness of a theoretical 10-mm airway. Trachea surface roughness shape (SRS) was calculated as the percent fraction of the measurement box filled by the surface mesh. Multivariable regression models were used to determine association for CT measurements with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and Medical Research Council dyspnea scale (MRC)≥3, adjusting for covariates. Results A total of 1253 participants (mean age, 66 ± 10 years; 727 men) from 9 centers were investigated: n = 267 never smokers, n = 369 ever smokers, n = 352 mild COPD, and n = 265 moderate-to-severe COPD. There were no differences between groups for age or race (P &amp;lt; .05). In models including SRS and TI, a 1-standard deviation (SD) increase in SRS was independently associated with a 0.11-SD decrease in FEV1 (β = –0.11; P &amp;lt; .001) and a 0.16-SD decrease in FEV1/FVC (β = –0.16; P &amp;lt; .001); a 1-point increase in SRS was associated with a 13% increased likelihood of MRC ≥ 3 (odds ratio = 1.13; P = .003). In models including SRS, low attenuation areas below –950 HU and wall thickness of a theoretical 10-mm airway, a 1-SD increase in SRS was associated with a 0.21-SD decrease in FEV1 (β = –0.21; P &amp;lt; .001) and a 0.13-SD decrease in FEV1/FVC (β = –0.13; P &amp;lt; .001); a 1-point increase in SRS was associated with a 12% increased likelihood of MRC ≥ 3 (odds ratio = 1.12; P = .006). Conclusion Increased trachea surface shape roughness is independently associated with worse airflow and increased symptom burden in COPD.

Spirometric Assessment of Pulmonary Function Tests in Asthma Patients.

Asthma is a chronic airway inflammatory disorder that imposes substantial morbidity and mortality. Spirometry is a significant tool for the objective measurement ofobstruction amongasthmatics. The present study was conducted to assess the pulmonary function test parameters among asthmatics and compare the observed and predicted values. This cross-sectional research was performed on 120 asthmatic patients who attended a tertiary care healthcare center and underwent spirometry evaluation. The spirometry indices such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, peak expiratory flow rate (PEFR), and maximal voluntary ventilation (MVV) were recorded. Further, a gender-wise comparisonof spirometry indices was also done. There was a substantial decrease in FVC (2.05 ± 0.12 vs. 2.75 ± 0.24 L/sec; p = 0.02), FEV1 (1.78 ± 0.16 vs. 2.38 ± 0.32 L/sec; p = 0.01), FEV1/FVCratio (74 ± 4.38 vs. 83 ± 5.76 %; p = 0.01), PEFR (4.76 ± 0.42 vs. 5.82 ± 0.65 L/sec; p = 0.03), and MVV (78.65 ± 28.45 vs. 115.87 ± 32.15 L/min; p = 0.001) for observed andpredicted values.Female asthmatic patients displayed a substantial decline in FVC (p = 0.001), FEV1 (p = 0.006), FEV1/FVC (p = 0.001), and MVV (p = 0.01) when compared to males. This study suggests that asthmatic individuals had impaired lung function upon initial assessment.Female asthmatic patients studied are at increased risk of asthma severity when compared to males.

Macrophage and CD8 T cell discordance are associated with acute lung allograft dysfunction progression

Acute lung allograft dysfunction (ALAD) is an imprecise syndrome denoting concern for the onset of chronic lung allograft dysfunction (CLAD). Mechanistic biomarkers are needed that stratify risk of ALAD progression to CLAD. We hypothesized that single cell investigation of bronchoalveolar lavage (BAL) cells at the time of ALAD would identify immune cells linked to progressive graft dysfunction. We prospectively collected BAL from consenting lung transplant recipients for single cell RNA sequencing. ALAD was defined by a ≥10% decrease in FEV1 not caused by infection or acute rejection and samples were matched to BAL from recipients with stable lung function. We examined cell compositional and transcriptional differences across control, ALAD with decline, and ALAD with recovery groups. We also assessed cell-cell communication. BAL was assessed for 17 ALAD cases with subsequent decline (ALAD declined), 13 ALAD cases that resolved (ALAD recovered), and 15 cases with stable lung function. We observed broad differences in frequencies of the 26 unique cell populations across groups (p=0.02). A CD8 T cell (p=0.04) and a macrophage cluster (p=0.01) best identified ALAD declined from the ALAD recovered and stable groups. This macrophage cluster was distinguished by an anti-inflammatory signature and the CD8 T cell cluster resembled a Tissue Resident Memory subset. Anti-inflammatory macrophages signaled to activated CD8 T cells via class I HLA, fibronectin, and galectin pathways (p<0.05 for each). Recipients with discordance between these cells had a nearly 5-fold increased risk of severe graft dysfunction or death (HR 4.6, 95% CI 1.1-19.2, adjusted p=0.03). We validated these key findings in 2 public lung transplant genomic datasets. BAL anti-inflammatory macrophages may protect against CLAD by suppressing CD8 T cells. These populations merit functional and longitudinal assessment in additional cohorts.

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Abdominal fat and risk of impaired lung function and asthma in children: A population‐based prospective cohort study

AbstractBackgroundObesity, specifically abdominal adiposity, is associated with increased risks of lung function impairment and asthma in children, but potential adverse effects among adolescents are unknown. We hypothesized that elevated amounts of specific abdominal fat depots during childhood and adolescence may lead to adverse respiratory outcomes in adolescents.MethodsIn a population‐based prospective cohort study among 2877 children at 13 years, we measured specific abdominal fat depots including subcutaneous fat mass and visceral fat mass by magnetic resonance imaging. Lung function was measured by spirometry, and current asthma by a questionnaire. Conditional regression analyses were used to examine the associations of abdominal fat depots with respiratory outcomes in adolescence.ResultsAfter adjustment for confounders and child's body mass index, higher subcutaneous and visceral fat mass index at age 13 years, independent of these measures at earlier age, were associated with lower FEV1, FEV1/FVC, and FEF75 (range Z‐score difference (95% CI): −0.10 (−0.15, −0.06) to −0.06 (−0.11, −0.01)). Also, an increase in subcutaneous and visceral fat between ages 10 and 13 years was associated with a decrease in FEV1, FEV1/FVC, and FEF75 during the same period. No associations of abdominal fat depots with asthma were observed.ConclusionAdolescents with higher amounts of subcutaneous and visceral fat, independent of that at an earlier age and body mass index, have an increased risk of lung function impairment.