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Introduction/Aim: Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease with marked clinical heterogeneity. This heterogeneity can be partly captured by clinical measures, such as the forced vital capacity (FVC) and ALS Functional Rating Scale‐Revised (ALSFRS‐R). We aimed to further characterize the performance of these clinical measures, including their independence and additivity, in predicting mortality. Methods: We leveraged the Pooled Resource Open‐Access ALS Clinical Trials (PRO‐ACT ALS) database, which includes data from 23 clinical trials (n = 2050). The primary exposures were baseline FVC and ALSFRS‐R. The primary outcome was 1‐y mortality. We performed correlation analyses, survival analyses and assessed classification performance using receiver operator characteristic (ROC) curves. Results: FVC and ALSFRS‐R were weakly correlated (r = 0.31, p <.001). A 1‐SD increase in FVC (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.59–0.74) and ALSFRS‐R (HR: 0.75; 95% CI: 0.68–0.82) were associated with reduced risk of 1‐y mortality. ROC analyses showed optimal predictive cutoffs at 80% for FVC (area under the curve [AUC]: 0.69) and 38 for ALSFRS‐R (AUC: 0.67). After stratifying patients based on these cutoffs, we found a marked reduction (HR: 0.25; 95% CI: 0.19–0.33) in incident mortality for patients in the high FVC and high ALSFRS‐R group relative to the low FVC and low ALSFRS‐R group. Discussion: ALSFRS‐R and FVC are comparable predictors of survival that are only weakly correlated. When considered together, they synergistically predict survival. As such, consideration of both measures should be a routine part of prognostication in care of patients with ALS. [ABSTRACT FROM AUTHOR]

The purpose of the study was to determine the effect of Specific Training Programme on Forced Vital Capacity and Forced Expiratory Volume of Rope Mallakhamb Players Aged 12 To 18 Years. The review of literature does not indicate any studies to evaluate the utility of Specific Training for the development of Forced Vital Capacity and Forced Expiratory Volumes of Rope Mallakhamb Players. Methodology and Design: A sample of Sixty (n=60) Rope Mallakhamb players age ranged from 12-18 years was identified as subjects from Mallakahamb Sangh Andheri area of Greater Mumbai. Further they were randomly divided into two equal groups i.e. experimental and control group with equal number of subjects. Experimental group is Specific Training Group (n=30) and Control group is Non Specific Training Group (n=30). The design of the study was Non-equivalent Control Group Design. The experimental subjects, along with day to day activity underwent through Specific Training programme for six days in a week except holiday. Materials and Method: At the baseline and after training intervention the Dependent variable i.e. Forced Vital Capacity and Forced Expiratory Volume test data were used for assessment. Statistical Analysis Used: Data were analyzed by using One Way ANCOVA test. Results: The results revealed that effect of Specific training programme helped to enhance Forced Vital Capacity and Forced Expiratory Volume of Rope Mallakhamb Players aged 12 to 18 years. [ABSTRACT FROM AUTHOR]

Introduction: Allergic rhinitis (AR) is a common IgE -mediated inflammatory condition characterised by sneezing, nasal congestion, itching and rhinorrhoea. Nasal allergy is a strong risk factor for the onset of asthma in adults. Bronchial hyper-responsiveness (BHR) is a distinct feature of pathophysiology in asthma. Spirometric parameters like Forced Expiratory Volume in first second [FEV1] and Forced Expiratory Flow [FEF 25–75%] are known to be impaired in patients with allergic rhinitis. We studied these parameters in subjects of AR who have never experienced any chest symptoms. It is well known that, subjects with allergic rhinitis are at greater risk of developing overt bronchial asthma in future. Methods: All patients presented with symptoms of allergic rhinitis without history of bronchial asthma were included. Patients those who were clinically diagnosed with allergic rhinitis were evaluated with absolute eosinophilic count, serum IgE and Spirometric assessment. In spirometry, post bronchodilator FEV1 reversibility and post bronchodilator FEF 25–75% values were used to assess lower airway abnormalities. Results: Among 61 subjects, 32 were males and 29 were females. The maximum numbers [28] of patients were in 21–35 age group. Absolute eosinophil count was elevated in 38% of patients. 33% of patients showed elevated IgE values above 1000. 43% of patients showed FEV1 reversibility which is a sign of Bronchial hyperreactivity. 5% of patients showed impaired post bronchodilator FEF 25–75% which indicates presence of small airway disease. There was significant correlation between FEV1 reversibility and elevated IgE. Conclusion: Impaired spirometric parameters indicate coexistence of bronchial impairment and hence predisposition to progression from allergic rhinitis alone to overt asthma in future. Thus careful evaluation of lower airway has to be done to rule out coexisting subclinical asthma.

Introduction: In slowly progressive myopathies, diaphragm weakness early manifests through sleep-related hypoventilation as reflected by nocturnal hypercapnia. This study investigated whether daytime tests of respiratory muscle function and diaphragm ultrasound predict hypercapnia during sleep.Methods: Twenty-seven patients with genetic myopathies (myotonic dystrophy type 1 and 2, late-onset Pompe disease, facioscapulohumeral dystrophy; 48 ± 11 years) underwent overnight transcutaneous capnometry, spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound.Results: Sixteen out of 27 patients showed nocturnal hypercapnia (peak ptcCO2 ≥ 50 mmHg for ≥ 30 min or increase in ptcCO2 by 10 mmHg or more from the baseline value). In these patients, forced vital capacity (FVC; % predicted) and maximum inspiratory pressure (MIP; % of lower limit or normal or LLN) were significantly reduced compared to normocapnic individuals. Nocturnal hypercapnia was predicted by reduction in FVC of 8.0 cm/s on diaphragm ultrasound.

Background: TAS-115, a novel multi-kinase inhibitor, demonstrated antifibrotic effects in vitro and in vivo. Methods: This is an open-label, intra-patient comparison, exploratory phase 2 study of TAS-115 to evaluate the efficacy and safety in idiopathic pulmonary fibrosis (IPF) patients when orally administered at 200 mg once daily on a 5-day on and 2-day off regimen for 13 weeks. This study consists of three cohorts: previously treated with pirfenidone (Cohort P, n = 20), with nintedanib (Cohort N, n = 20), and treatment naïve (Cohort U, n = 10). Male or female patients aged ≥40 to

Background: Clinical course of pleuroparenchymal fibroelastosis (PPFE) shows considerable variation among patients, but there is no established prognostic prediction model for PPFE.Methods: The prediction model was developed using retrospective data from two cohorts: our single-center cohort and a nationwide multicenter cohort involving 21 institutions. Cox regression analyses were used to identify prognostic factors. The total score was defined as the weighted sum of values for the selected variables. The performance of the prediction models was evaluated by Harrell's concordance index (C-index). We also examined the usefulness of the gender-age-physiology (GAP) model for predicting the prognosis of PPFE patients.Results: We examined 104 patients with PPFE (52 cases from each cohort). In a multivariate Cox analysis, a lower forced vital capacity (FVC [defined as FVC < 65%]; hazard ratio [HR], 2.23), a history of pneumothorax (HR, 3.27), the presence of a lower lobe interstitial lung disease (ILD) (HR, 2.31), and higher serum Krebs von den Lungen-6 (KL-6) levels (> 550 U/mL, HR, 2.56) were significantly associated with a poor prognosis. The total score was calculated as 1 × (FVC, < 65%) + 1 × (history of pneumothorax) + 1 × (presence of lower lobe ILD) + 1 × (KL-6, > 550 U/mL). PPFE patients were divided into three groups based on the prognostic score: stage I (0-1 points), stage II (2 points), and stage III (3-4 points). The survival rates were significantly different in each stage. The GAP stage was significantly associated with the prognosis of PPFE, but no difference was found between moderate (stage II) and severe (stage III) disease. Our new model for PPFE patients (PPFE Prognosis Score) showed better performance in the prediction of mortality in comparison to the GAP model (C-index of 0.713 vs. 0.649).Conclusions: Our new model for PPFE patients could be useful for predicting their prognosis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of rituximab (RTX), an antiB cell monoclonal antibody, on lung and skin involvement in systemic sclerosis (SSc). Methods: All literature published in Embase and Medline before September 2019 were comprehensively searched. Two independent reviewers selected eligible studies, extracted relevant data, and assessed the quality of the included studies. We only considered randomized, controlled trials (RCTs), cohort studies, and case-control studies that compared RTX with a placebo, other immunosuppressive agents, or corticosteroids. All analyses were performed using RevMan (version 5.3). Results: A total of 8 studies (3 RCTs and 5 cohort studies) met our inclusion criteria. The pooled analysis showed a significant improvement of modified Rodnan skin score in the RTX group only in the cohort studies (mean difference [SD] − 3.31 [− 4.95, − 1.68]; I2 = 82%). As to the PFT, the RTX group showed a significant improvement in the forced vital capacity only in 3 RCTs (mean difference [SD] 6.59 [3.51, 9.68]; I2 = 0%). Additionally, the RTX group demonstrated a statistically significant improvement in the diffuse capacity of carbon monoxide only in the cohort studies (mean difference [SD] 7.42 [1.08, 13.76]; I2 = 97%). There were no significant differences in the AEs of the RTX and control groups. Conclusions: RTX may be effective for lung and skin involvement in SSc, with no serious AEs. However, further studies with high quality and a large sample size are necessary to firmly establish the efficacy and safety of the use of RTX with SSc patients. Key Points • RTX may be an alternative treatment for cutaneous and pulmonary manifestations in patients with SSc with a favorable safety profile. • However, further studies with a high quality and large sample size are necessary to firmly establish its efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Among the vital functions, respiration can be claimed to be one of the most important. A thorough understanding of the patient should be an important aspect a prosthodontist should dwell into so as to predispose patients to acknowledge the kind of prosthesis they require. Hence, the present study was conducted for assessing the effect of complete dentures on respiratory performance. Materials and Methods: Fifty patients with the presence of complete edentulous arch and who had a history of complete denture usage for at least 5 years were enrolled. All the spirometric procedures were performed by trained technicians. A diagnostic spirometer was employed for performing the spirometric test. Testing was carried out in the following steps: Stage 1: testing in the absence of denture, Stage 2: testing in the presence of both dentures, Stage 3: testing in the presence of maxillary denture only, and Stage 4: testing in the presence of mandibular dentures only. Forced vital capacity (FVC) value, peak expiratory flow (PEF) value, forced expiratory volume in 1 s (FEV1) value, and forced expiratory flow 25%-75% (FEF25-75) value were recorded with the spirometric test. Analysis of all the results was done by SPSS software. Results: The spirometric value of FVC, PEF, FEV1, and FEF25-75 in the absence of both maxillary and mandibular dentures (Stage 1) was found to be 3.18, 5.83, 2.44, and 2.80, respectively. The spirometric value of FVC, PEF, FEV1, and FEF25-75 in the presence of both maxillary and mandibular dentures (Stage 2) was found to be 3.09, 5.67, 2.41, and 2.67, respectively. While analyzing statistically, it was seen that there was a significant decrease in the value of spirometric variables in the presence of dentures. Conclusion: Chronic denture wearer edentulous patients are subjected to the risk of development of spirometric alterations. Hence, these patients should be given timely instructions about the various respiratory exercise protocols. [ABSTRACT FROM AUTHOR]

Background: Among the vital functions, respiration can be claimed to be one of the most important. A thorough understanding of the patient should be an important aspect a prosthodontist should dwell into so as to predispose patients to acknowledge the kind of prosthesis they require. Hence, the present study was conducted for assessing the effect of complete dentures on respiratory performance. Materials and Methods: Fifty patients with the presence of complete edentulous arch and who had a history of complete denture usage for at least 5 years were enrolled. All the spirometric procedures were performed by trained technicians. A diagnostic spirometer was employed for performing the spirometric test. Testing was carried out in the following steps: Stage 1: testing in the absence of denture, Stage 2: testing in the presence of both dentures, Stage 3: testing in the presence of maxillary denture only, and Stage 4: testing in the presence of mandibular dentures only. Forced vital capacity (FVC) value, peak expiratory flow (PEF) value, forced expiratory volume in 1 s (FEV1) value, and forced expiratory flow 25%–75% (FEF25–75) value were recorded with the spirometric test. Analysis of all the results was done by SPSS software. Results: The spirometric value of FVC, PEF, FEV1, and FEF25–75 in the absence of both maxillary and mandibular dentures (Stage 1) was found to be 3.18, 5.83, 2.44, and 2.80, respectively. The spirometric value of FVC, PEF, FEV1, and FEF25–75 in the presence of both maxillary and mandibular dentures (Stage 2) was found to be 3.09, 5.67, 2.41, and 2.67, respectively. While analyzing statistically, it was seen that there was a significant decrease in the value of spirometric variables in the presence of dentures. Conclusion: Chronic denture wearer edentulous patients are subjected to the risk of development of spirometric alterations. Hence, these patients should be given timely instructions about the various respiratory exercise protocols. [ABSTRACT FROM AUTHOR]

BACKGROUND: Subjects with thoracic scoliosis were an important group in early studies of noninvasive ventilation (NIV). The aim of this study was to describe current rates of initiation of NIV and survival after initiation in this population. METHODS: This study included patients identified as having thoracic scoliosis and established between 1993 and 2018 on home NIV. Patients with scoliosis secondary to neuromuscular disease (other than poliomyelitis) were excluded. Survival rates were calculated for various time intervals up to 25 y. RESULTS: A total of 53 subjects with thoracic scoliosis were successfully established on NIV. PaCO2 levels prior to starting NIV were 55 « 23 mm Hg. FVC was 0.5 « 0.1 L, 18.5 « 9% of predicted, with a Cobb angle of 101 « 3.5 degrees. The 5-, 10-, 15-, 20-, and 25-y survival rates were 96%, 88%, 61%, 46%, and 39%, respectively. At the time of death, subjects had been on home NIV for 9.2 « 5.1 y and were 75.5 « 9.2 y old. There was no significant correlation between mortality and age at time of commencing home NIV, initial arterial blood gas results, FVC, or Cobb angle. There was no significant difference in survival between those with and without poliomyelitis. In 8 of 10 of the most recent years of this survey, subjects with scoliosis have been commenced on home NIV. CONCLUSIONS: Small numbers of subjects with scoliosis continued to present with respiratory failure. Once established on home NIV, around 40% survived ≤ 25 y. Long-term care will be needed for many years to come for this patient population. [ABSTRACT FROM AUTHOR]

Phthalates can leach into indoor and outdoor airborne particulate matter and dust, which can then be ingested or absorbed and induce lung injury. Dermal phthalate levels can be used as a matrix for exposure direct absorption from air, particle deposition, and contact with contaminated products. However, the association between dermal phthalate levels in skin wipes and lung function tests remains unknown. A total of 397 participants were included. Spirometry measurements of forced expiratory volume in 1 s (FEV1, L) and forced vital capacity (FVC, L) were calculated. Dermal phthalate levels of diethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP) on forehead skin wipes were detected. The one-unit increases in logarithm (log) dermal DnBP (β = − 0.08; 95% CI − 0.16, − 0.003, p = 0.041), BBzP (β = − 0.09; 95% CI − 0.16, − 0.02, p = 0.009), DEHP (β = − 0.07; 95% CI − 0.14, − 0.003, p = 0.042), and DiNP (β = − 0.08; 95% CI − 0.15, − 0.02, p = 0.017) were significantly associated with decreases in FVC. For elderly participants, one-unit increases in log dermal DnBP (β = − 0.25; 95% CI − 0.46, − 0.04, p = 0.021), BBzP (β = − 0.17; 95% CI − 0.33, − 0.01, p = 0.042), and DiDP (β = − 0.19; 95% CI − 0.39, < 0.01, p = 0.052) were associated with decreases in FEV1. In conclusion, dermal phthalate levels were significantly associated with decreases in lung function tests. [ABSTRACT FROM AUTHOR]

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown.Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF.Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization's registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen's d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM).Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83).Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment. [ABSTRACT FROM AUTHOR]

Spirometer is used as a major diagnostic tool for obstructive airway diseases and a monitoring tool for therapy response and disease staging over time. It is a sophisticated medical device employed to quantify flow and volume of air exhaled by a subject during a specific testing period. The essential metrics obtained from the spirometry test, play a crucial role in enabling healthcare professionals to thoroughly evaluate the respiratory health and condition of the individual under examination. Several spirometer measurements including Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV) serve as guidelines for diagnosis and prognosis of Chronic Obstructive Pulmonary Diseases (COPD) and asthma. However, user errors caused by different reasons, including improper handling of the equipment and poor performance during the maneuvers of the expiratory airflow, end up in incorrect treatment directions. To ensure accurate results, spirometry tests traditionally require the presence of a skilled professional to identify and address these errors promptly. A novel machine learning approach is proposed in this paper to automatically identify four such user errors based on Volume-Time and Flow-Volume graphs. By detecting specific errors and providing immediate feedback to patients, reliability and accuracy of spirometry results will be improved and the need for trained professionals will be reduced. The implementation facilitates the widespread adoption of spirometry, particularly in low-resource telemedicine settings. This work implements a binary classification model distinguishing between normal and error test samples, achieving a prediction accuracy of 93%. Additionally, a 4-way classification model is presented for identifying individual error sub-types, demonstrating a prediction accuracy of 94%. • Errors: Early Terminus, Extra Breath, Excessive Extrapolated Volume, SubMaximal Blast • Flattening and concatenation of 2 CNN Pipelines, one each for FV and VT graph inputs • Stratified 5-fold CV on categorical cross entropy loss and leaky ReLU activation unit • Error detection model - 93% accuracy and error classification model - 94% accuracy [ABSTRACT FROM AUTHOR]

Introduction: Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma. Methods: We explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined < 100% and ≥ 1.0 kPa/L/s as impaired FVC or AX, respectively. Results: Patients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV1 and FEF25–75) than those with impaired FVC but preserved AX. Conclusion: This in turn supports using both spirometry and oscillometry to characterise airway physiology more comprehensively in patients with more severe asthma. [ABSTRACT FROM AUTHOR]

Abstract Purposes Hip fracture leads to decreased activity and an increased risk of pulmonary complications. The main purpose of this study was to observe the lung capacity, cough capacity of the elderly patient with acute hip fracture, and assess the effects and the feasibility of using a special-designed “upper-body yoga” training to treat elderly patients with hip fracture. Methods This was a prospective, randomized, and single-blind study. Eighty-four subjects aged over 65 years were randomly divided into either a control group or a yoga group to undergo an abdominal breathing program or an “upper-body yoga” program until 4 weeks after surgery. The primary outcomes were forced vital capacity/predicted value (FVC%), peak cough flow (PCF), Barthel Index (BI), and the incidence of pneumonia. The secondary outcomes were the rates of right skills and inclination. Results Thirty-nine subjects in the yoga group and 40 subjects in the control group completed this study. At the end of the first training week, FVC% (74.14% ± 13.11% vs. 70.87% ± 10.46%, P = 0.231) showed no significant difference between the two groups, while the value of PCF (204.80 ± 33.45 L/min vs. 189.06 ± 34.80 L/min, P = 0.048) and BI (38.59 ± 8.66 vs. 33.00 ± 9.32, P = 0.009) in the yoga group was higher. After 4 weeks of treatment, FVC%, PCF, and BI were higher in the yoga group (78.83% ± 13.31 % vs. 72.20% ± 10.53%, P = 0.016; 216.16 ± 39.29 L/min vs. 194.95 ± 31.14 L/min, P = 0.008; 70.77 ± 10.23 vs. 65.75 ± 11.30, P = 0.019). One in the control group and nobody in the yoga group was diagnosed with pneumonia. There was no significant difference between the two groups in terms of the rates of right skills, whereas more elderly people preferred the training program of the “upper-body yoga.” Conclusion Elderly patients with acute hip fractures are at risk of impaired lung capacity and inadequate cough. “Upper-body yoga” training may improve the quality of daily life, vital capacity, and cough flow in elderly patients, making it a better choice for bedridden patients with hip fracture.

Background Thalassemia is a challenging health problem all over the world, especially in Mediterranean areas. Its effect on pulmonary function has not been well studied. Aim of the work To describe pulmonary function changes in patients with β-thalassemia major. Patients and methods This study included 60 patients with β-thalassemia major who received regular blood transfusion (40 males and 20 females) and 30 control children (20 males and 10 females). All participants were subjected to full history taking, clinical examination, and laboratory investigations (complete blood count, serum iron, and serum ferritin). In addition, all underwent pulmonary function tests. Results Forced expiratory volume at first second, forced vital capacity, and forced expiratory flow 25–75% were significantly decreased in males and females in the patient group when compared with those in the control group. However, forced expiratory volume at first second/forced vital capacity was significantly increased in male and female patients when compared with those in the control group. Transfusion and chelation therapy seems to be the cause of reduced pulmonary function. Conclusion Children with β-thalassemia had reduced pulmonary function, and this could be attributed to chelation therapy that affects serum iron and ferritin.

Context: Liuweibuqi (LWBQ) capsule has been reported to influence symptoms of patients with chronic obstructive pulmonary disease (COPD); however, specific function of LWBQ capsules in COPD with lung-qi deficiency syndrome remains elusive. Objective: This study investigates effect of LWBQ capsules on STAT4/STAT6 and MMP-9/TIMP-1 expression and pulmonary function in stable COPD with lung-qi deficiency syndrome. Materials and methods: Totally, 429 patients diagnosed with stable COPD and lung-qi deficiency syndrome were treated with starch capsules (each time for 9 capsules), or different doses: low (each dose for 8 capsules and 1 LWBQ capsules), medium (each time for 6 capsules and 3 LWBQ capsules), or high (each time for 9 LWBQ capsules) of LWBQ capsules for 30 days, 3 times a day. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% and DLco%pred were evaluated by pulmonary function meter. STAT4/STAT6 and MMP-9/TIMP-1 expression was assessed by RT-qPCR and western blot analysis, and serum concentrations of IL-4, IFN-γ and IL-6 by ELISA. Results: Spearman rank correlation analysis and ROC curve showed that STAT4/STAT6 and MMP-9/TIMP-1 affected pulmonary functions and curative effect of stable COPD with lung-qi deficiency syndrome. After LWBQ capsule treatment, FEV1, FVC, FEV1/FVC% and DLco%pred elevated; STAT4/STAT6, MMP-9/TIMP-1, IFN-γ and IL-6 expression declined whereas IL-4 expression increased (p

Background and Aim: Formaldehyde exposure is one of the various occupational hazards experienced by a doctor during his life. There is consistent and regular exposure to formaldehyde during the gross anatomy dissection classes. Since it vaporizes at room temperature, respiratory system is easily affected. The present study was undertaken to assess its effect on forced vital capacity (FVC) of medical students. The aim of this study is to evaluate the FVC of the 1st year medical students after exposure to formaldehyde. Materials and Methods: A longitudinal study was conducted in the Department of Physiology among 1st year MBBS students. The spirometric parameter FVC was recorded in 80 medical students using spirometer RMS Helios 401. Percent predicated values were used for analysis. The baseline values were recorded at the beginning of the academic calendar and followed up at the end of 1st, 6th, and 10th months. Data were analyzed using the SPSS. Descriptive statistics and repeated measures ANOVA was used for the analysis. A value of P < 0.05 was considered statistically significant. Results: The mean FVC declined significantly over the 1st month of exposure following which there was a gradual reversion to the baseline values over the remaining study period. The cumulative pattern of this change was also statistically significant (P = 0.000). Conclusion: Formaldehyde causes detrimental changes on the ventilatory mechanics of the lung. The effect is marked in the initial phase following which the body tries to restore homeostasis.

Background: Skeletal muscle dysfunction is well known in chronic obstructive pulmonary disease (COPD). The muscle strength is altered in various muscles variedly. Lower-limb muscle strength is very important for walking distance. Reduced lower-limb strength can affect the physical quality of life. Objectives: The aim of the study was to assess and compare the quadriceps strength in COPD patients and age-matched healthy controls and to study the correlation between lung function parameters and the quadriceps strength in patients with COPD. Methodology: Thirty nonsmoker male patients; thirty nonsmoker female patients with COPD; and sixty age-, BMI-, and gender-matched healthy controls were studied. Quadriceps muscle strength was measured using a quadriceps dynamometer. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEF 25–75, and peak expiratory flow rate were measured using Helios 702 Spirometer. The quadriceps muscle strength between the two groups was compared using the unpaired Student's t-test. Correlations between FVC and FEV1with muscle strength were analyzed using the Pearson's coefficient. Results: The mean unilateral and bilateral quadriceps strength in both male and female COPD patients was significantly lesser than the healthy controls (P < 0.05). There was a significant positive correlation between muscle strength and FVC and muscle strength and FEV1in patients with COPD. Conclusion: The study shows that there is quadriceps weakness in COPD patients, and pulmonary functions have a direct impact on skeletal muscle strength. Identifying those patients who have reduced strength will allow early interventions targeted at improving the quality of life of the patient.

BackgroundA multicenter study of pectus excavatum was described previously. This report presents our final results.Study designPatients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing.ResultsOf 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), 18% had late complications, similarly distributed, including substernal bar displacement in 7% and wound infection in 2%. Mean initial CT scan index of 4.4 improved to 3.0 post operation (severe >3.2, normal = 2.5). Computed tomography index improved at the deepest point (xiphoid) and also upper and middle sternum. Pulmonary function tests improved (forced vital capacity from 88% to 93%, forced expiratory volume in 1 second from 87% to 90%, and total lung capacity from 94% to 100% of predicted (p < 0.001 for each). VO2 max during peak exercise increased by 10.1% (p = 0.015) and O2 pulse by 19% (p = 0.007) in 20 subjects who completed both pre- and postoperative exercise tests.ConclusionsThere is significant improvement in lung function at rest and in VO2 max and O2 pulse after surgical correction of pectus excavatum, with CT index >3.2. Operative correction significantly reduces CT index and markedly improves the shape of the entire chest, and can be performed safely in a variety of centers.

Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort.Methods: A total of 209 asthmatic children within 5–13 years old were included and divided into reduced FVC (“restricted,” n = 66) and typical obstruction group (“obstructed,” n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%).Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = −0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = −0.349, P = 0.012) and with FEF25−75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04–1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25−75% z-score (n = 29, r = −0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05).Conclusion: These findings suggested that “poor FVC effort” does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.

Introduction: In this study, we aimed to evaluate diaphragmatic dysfunction (DD) by using a practical approach in patients with amyotrophic lateral sclerosis (ALS) at the first visit to a chest diseases outpatient clinic.Methods: Patients with ALS seen in our outpatient clinic for the past 5 y and followed up for at least 1 y, were retrospectively evaluated. Having at least one of the following three criteria was accepted as DD: (a) paradoxical abdominal movement (PAM), (b) sitting-supine forced vital capacity (FVC) difference ≥ 20%, (c) sitting-supine arterial oxygen saturation measured by pulse oximetry (SpO2 ) difference ≥ 4%. Respiratory symptoms, arterial blood gas analysis, sleep studies, noninvasive mechanical ventilation use, and mortality were recorded.Results: Five-hundred patients with ALS were included (female/male: 220/280, age: 58.9 ± 11.3 y). Of the patients, 22.8% had daytime hypercapnia. DD was observed in 55% of the patients (PAM in 112, sitting-supine FVC difference ≥ 20% in 50, and sitting-supine SpO2 difference ≥ 4% in 113 patients). Of the patients with DD, 31.6% (n = 87) had no respiratory symptoms, 46.4% had FVC > 70% and 33.5% had FVC <50%. Nocturnal hypoxemia (sleep time spent with SpO2  < 90% ≥30%) was present in 59.7%, and all patients with nocturnal hypoxemia had DD. Obstructive sleep apnea (8 severe, 14 moderate, 39 mild) was detected in 55% of the patients with polysomnography (n = 61) or polygraphy (n = 50). During follow-up, 52.2% of the patients died. Mean survival time was shorter in patients with DD (P < .001).Conclusion: Paradoxical abdomimal movement (PAM), sitting-supine SpO2 difference ≥ 4% and sitting-supine FVC difference ≥ 20% are indicators of DD, which should be routinely evaluated at every outpatient visit. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It has been suggested that Vitamin D Deficiency (VDD) worsens lung functions and COPD lowers vitamin D levels, but this has not been proven yet. MATERIAL AND METHODS: The study was carried out between January 2014 and September 2015. All the COPD patients with 25 (OH) D3 measurements were included in this study. The patients < 40-year-old, or with a smoking history of less than 10 package-year, or with asthma, bronchiectasis, pneumonia, tuberculosis, cancer, were excluded from the study. Medical records about age, gender, pulmonary function test, body mass index (BMI), annual exacerbations/hospitalizations, modified British Medical Research Council (mMRC) level and serum 25 (OH) D3 were obtained. RESULTS: The data of 216 (83.8% male) patients were examined in the study. The mean age was 66.88 ± 10.3 years. The mean vitamin D level was 21.1 ± 13.73 ng/mL. Of the patients, 57.9% had VDD, and even 19.9% were in severe VDD. Only 26.4% had adequate vitamin D level. There was a significant in BMI, FEV1, FVC, annual exacerbation and hospitalisations between the patients with vitamin D levels > 20 ng / mL and ≤ 20 ng / mL. Vitamin D level of patients with mMRC level 1 was significantly higher than those with mMRC 2, 3, 4 (respectively P = .03; P = .026; P = .014). CONCLUSION: In this study, we found that lung function was worse in COPD patients with VDD and VDD increased with increasing severity of COPD. [ABSTRACT FROM AUTHOR]

Introduction: Sarcoidosis is a systemic granulomatous disease of unknown cause afflicting young to middle-aged adults. The majority of patients with active pulmonary sarcoidosis complain of overwhelming fatigue, which often persists despite administration of immune-modulating drugs typically used to treat sarcoidosis. Nicotine offers an alternative to conventional treatments, which are associated with a spectrum of serious untoward effects, including diabetes mellitus, osteoporosis, bone marrow suppression, severe infections, cirrhosis. The described pilot randomized trial aims to provide preliminary data required to design subsequent Phase II/III trials to formally evaluate nicotine as a novel low-cost and highly-effective, safe treatment option for patients with active pulmonary sarcoidosis. Methods: and Design: This is a randomized double-blind controlled trial of adults with confirmed pulmonary sarcoidosis, allocated in equal proportion to sustained release transdermal nicotine or placebo patch. The primary objective outcome is the improvement in forced vital capacity at study week 26 from baseline measurement. Secondary measures include lung texture score, and self-reported outcomes including the Fatigue Assessment Scale, the St George's Respiratory Questionnaire, and the Sarcoidosis Assessment Tool. Discussion: Current therapies for active pulmonary sarcoidosis, remain either expensive and often with numerous side-effects, as with novel industry developed therapies, or with reduced quality of life, as with corticosteroids. Nicotine therapy provides promise as a safe, available, and cost-effective intervention strategy, which we expect to be acceptable to patients. ClinicalTrials.gov: NCT02265874.

BackgroundTiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.ObjectiveWe sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.MethodsData from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).ResultsAlthough approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.ConclusionAlthough these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

Antioxidant enzymes play an important role in the defense against oxidative stress in the lung and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sequence variation in genes encoding antioxidant enzymes may alter susceptibility to COPD by affecting longitudinal change in lung function in adults. We genotyped 384 sequence variants in 56 candidate genes in 1281 African American and 1794 European American elderly adults in the Health, Aging, and Body Composition study. Single-marker associations and gene-by-smoking interactions with rate of change in FEV₁ and FEV₁/FVC were evaluated using linear mixed-effects models, stratified by race/ethnicity. In European Americans, rs17883901 in GCLC was statistically significantly associated with rate of change in FEV₁/FVC; the recessive genotype (TT) was associated with a 0.9% per year steeper decline (P = 4.50 × 10(-5)). Statistically significant gene-by-smoking interactions were observed for variants in two genes in European Americans: the minor allele of rs2297765 in mGST3 attenuated the accelerated decline in FEV₁/FVC in smokers by 0.45% per year (P = 1.13 × 10(-4)); for participants with greater baseline smoking pack-years, the minor allele of rs2073192 in IDH3B was associated with an accelerated decline in FEV₁/FVC (P = 2.10 × 10(-4)). For both genes, nominally significant interactions (P < 0.01) were observed at the gene level in African Americans (P = 0.007 and 4.60 × 10(-4), respectively). Nominally significant evidence of association was observed for variants in SOD3 and GLRX2 in multiple analyses. This study identifies two novel genes associated with longitudinal lung function phenotypes in both African and European Americans and confirms a prior finding for GCLC. These findings suggest novel mechanisms and molecular targets for future research and advance the understanding of genetic determinants of lung function and COPD risk.

BackgroundRecent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function.ObjectiveWe sought to identify novel lung function loci specifically for asthma and to confirm lung function loci identified in general populations.MethodsGenome-wide association studies of lung function (percent predicted FEV1 [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses.ResultsSeven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10(-4)) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10(-11)). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10(-7)) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function.ConclusionGenes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility.

Objective To investigate the potential contribution of accessory respiratory muscle atrophy to the decline of forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease (ILD). Methods This single-centre, retrospective study enrolled 36 patients with SSc-ILD who underwent serial pulmonary function tests and chest high-resolution CT (HRCT) simultaneously at an interval of 1–3 years. The total extent of ILD and chest wall muscle area at the level of the ninth thoracic vertebra on CT images were evaluated by two independent evaluators blinded to the patient information. Changes in the FVC, ILD extent, and chest wall muscle area between the two measurements were assessed in terms of their correlations. Multiple regression analysis was conducted to identify the independent contributors to FVC decline. Results Interval changes in FVC and total ILD extent were variable among patients, whereas chest wall muscle area decreased significantly with time (P= 0.0008). The FVC change was negatively correlated with the change in ILD extent (r = − 0.48, P= 0.003) and was positively correlated with the change in the chest wall muscle area (r  = 0.53, P= 0.001). Multivariate analysis revealed that changes in total ILD extent and chest wall muscle area were independent contributors to FVC decline. Conclusion In patients with SSc-ILD, FVC decline is attributable not only to the progression of ILD but also to the atrophy of accessory respiratory muscles. Our findings call attention to the interpretation of FVC changes in patients with SSc-ILD. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. These processes play the main role in causing impairments of collagen & elastin cross linkage, which thereby causes reduced elasticity of connective tissue. The presence of abundant connective tissue and micro-vascular circulation in lung raises the possibility that in diabetic patients, lung could also be a "target organ".Pulmonary function test is a useful test to assess involvement of lung connective tissues and micro vascular bed in diabetic patients. Methods: In this study, which was conducted in a tertiary care hospital of South Gujarat, we enrolled 65 subjects who were known cases diabetes mellitus. Result: Diabetes Mellitus in patients alters Various parameters of PFT like FVC, FEV1 which are reduced while FEV1/FVC increased showed restrictive pattern compared to normal individual. Conclusion: Diabetes mellitus patients have positive correlation with interpretation of PFT as with HbA1c increases a greater number of patients develop abnormal PFT in which Restrictive pattern is seen more commonly. [ABSTRACT FROM AUTHOR]

Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases (ILD). Both drugs have side effects that affect patients in different ways and have different levels of severity, making treatment even more challenging for patients and clinicians. The present review aims to assess the effectiveness and potential complications of Pirfenidone and Nintedanib treatment regimens across various ILD diseases. A detailed search was performed in relevant articles published between 2018 and 2023 listed in PubMed, UpToDate, Google Scholar, and ResearchGate, supplemented with manual research. The following keywords were searched in the databases in all possible combinations: Nintedanib; Pirfenidone, interstitial lung disease, and idiopathic pulmonary fibrosis. The most widely accepted method for evaluating the progression of ILD is through the decline in forced vital capacity (FVC), as determined by respiratory function tests. Specifically, a decrease in FVC over a 6-12-month period correlates directly with increased mortality rates. Antifibrotic drugs Pirfenidone and Nintedanib have been extensively validated; however, some patients reported several side effects, predominantly gastrointestinal symptoms (such as diarrhea, dyspepsia, and vomiting), as well as photosensitivity and skin rashes, particularly associated with Pirfenidone. In cases where the side effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. However, further research is needed to optimize the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. Finally, other studies are requested to establish the treatments that can stop ILD progression.

Diver training improves physical and mental fitness, which can also benefit other sports. This study investigates the effect of eight weeks of static apnea training on maximum apnea time, and on the physiological parameters of runners, swimmers, and sedentary participants, such as forced vital capacity (FVC), minimum heart rate (HR), and oxygen saturation (SpO 2 ). The study followed 19 participants, including five runners, swimmers, sedentary participants, and four competitive divers for reference values. The minimum value of SpO 2 , HR, maximum duration of apnea, and FVC were measured. Apnea training occurred four times weekly, consisting of six apneas with 60 s breathing pauses. Apnea duration was gradually increased by 30 s. The measurement started with a 30 s apnea and ended with maximal apnea. There was a change in SpO 2 decreased by 6.8%, maximum apnea length increased by 15.8%, HR decreased by 9.1%, and FVC increased by 12.4% for the groups ( p < 0.05). There were intra-groups changes, but no significant inter-groups difference was observed. Eight weeks of apnea training improved the maximum duration of apnea, FVC values and reduced the minimum values of SpO 2 and HR in all groups. No differences were noted between groups after training. This training may benefit cardiorespiratory parameters in the population.

Background: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices., Methods: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV 1 /FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers., Results: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV 1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV 1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV 1 /FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices., Conclusion: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma., Trial Registration: CTRI/2021/09/036492 (Clinical Trials Registry - India)., (© 2024. The Author(s).)

Background: The relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial., Objective: This study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy., Methods: First, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses., Results: In the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors., Conclusion: Our results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Chang, Lian, Chen, Wang and Fu.)

Background and Purpose: Pompe disease is a rare, inheritable, progressive metabolic myopathy. This study aimed to estimate the minimal clinically important difference (MCID) for an improvement in forced vital capacity in the upright seated position (FVC up ) and the 6-min walk test (6MWT) after a year of treatment with enzyme replacement therapy., Methods: Data were obtained from two prospective follow-up studies. Between-group and within-group MCIDs were estimated using anchor-based methods. Additionally, a distribution-based method was used to generate supportive evidence. As anchors, self-reported change in health and in physical functioning, shortness of breath and a categorization of the Short-Form 36 Physical Component Summary score were used. Anchor appropriateness was assessed using Spearman correlations (absolute values ≥0.29) and a sufficient number of observations in each category., Results: In all, 102 patients had at least one FVC up or 6MWT measurement during enzyme replacement therapy. Based on the anchors assessed as appropriate, the between-group MCID for an improvement in FVC up ranged from 2.47% to 4.83% points. For the 6MWT, it ranged from 0.35% to 7.47% points which is equivalent to a distance of 2.18-46.61 m and 1.97-42.13 m for, respectively, a man and a woman of age 50, height 1.75 m and weight 80 kg. The results of the distribution-based method were within these ranges when applied to change in the outcome values., Conclusion: The MCIDs for FVC up and 6MWT derived in this study can be used to interpret differences between and within groups of patients with Pompe disease in clinical trials and cohort studies., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis (IPF) who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with IPF in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with IPF were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every 4 weeks. The primary endpoint was absolute change from baseline to Week 52 in FVC. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted FVC and 6-minute walk distance. Safety was monitored via adverse events. Post hoc analysis of the phase II and phase III data explored changes in FVC and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early after a prespecified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in FVC was similar between placebo and zinpentraxin alfa (-214.89 ml and -235.72 ml; P  = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced one or more adverse events. Post hoc analysis revealed that extreme FVC decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with IPF over placebo. Learnings from this program may help improve decision making around trials in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04552899).

Objective: Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV 1 ] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV 1 )., Results: Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV 1 :FVC ratio and 23,729 values for FEV 1 . A ratio of FEV 1 :FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV 1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background/objective: Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue., Methods: We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models., Results: Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood ( p  < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, p  = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p  < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, p  = 0.005)., Conclusion: The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects., Competing Interests: CW has received honoraria from Biogen as an advisory board member and for lectures and as an advisory member and consultant from Hoffmann-La Roche. She also received travel expenses from Biogen. AL received financial research support from AB Science, Biogen Idec, Cytokinetics, GSK, Orion Pharam, Novartis, TauRx Therapeutics Ltd. and TEVA Pharmaceuticals. He also has received honoraria as a consultant from Mitsubishi, Orion Pharma, Novartis, Teva and as an advisory board member of Biogen, Treeway, and Hoffmann-La Roche. ZU has received honoraria from Biogen as a consultant. JDo has received honoraria from Biogen for lectures. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wurster, Uzelac, Dreyhaupt, Schuster, Dorst, Ludolph and Wollinsky.)

Background “Quantile-dependent expressivity” refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and the FEV1/FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability (h2) is constant over all quantiles of their distribution. Methods Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (βOP), offspring-midparent (βOM), and full-sib regression slopes (βFS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βOPs were used as simple indicators of quantile-specific heritability (i.e., h2 = 2βOP/(1+rspouse), where rspouse was the correlation between spouses). Results βOP ± standard error (SE) decreased by 0.0009 ± 0.0003 (P = 0.003) with every one-percent increment in the population distribution of FEV1/FVC, i.e., βOP ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV1/FVC distribution, respectively. These correspond to h2 ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV1/FVC ratio. Maximum mid-expiratory flow (MMEF) h2 ± SEs increased 0.0025 ± 0.0007 (P = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific h2 increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific h2, i.e., greater heritability in individuals with lower FEV1/FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals. Conclusion Heritabilities of FEV1/FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.

Depression is known to be correlated with increased risk for chronic obstructive pulmonary disease (COPD) in middle-aged and older adults, but there is scarce evidence regarding its association with lung function among healthy adults. Thus, we aimed to assess this association by measuring the lung function and depression severity in Chinese college students. This cross-sectional study was conducted among 3,891 college students aged 16–24 years. Lung function was assessed by measuring the forced vital capacity (FVC) using a spirometer, and depression severity was evaluated using the 20-item Zung self-rating depression scale (SDS), with SDS scores of ≥40 and ≥45 indicating mild and moderate-to-severe depression, respectively. After adjusting for potential confounders, the geometric means of the FVC levels for the normal, mild depression, and moderate-to-severe depression groups were 3,446.1 (95% confidence interval [CI]: 3,418.6–3,470.3), 3,415.2 (95% CI: 3,357.7–3,473.8), and 3,351.0 (95% CI: 3271.5–3432.3), respectively (P for trend: 0.031). These results indicated that depression severity was independently correlated with lung function decline in Chinese college students. Future prospective cohort or interventional studies are needed to confirm the negative association between depressive symptoms and lung function and investigate its causality.

Mitsuhiro Abe,1 Kenji Tsushima,1,2 Masashi Sakayori,1 Kenichi Suzuki,1 Jun Ikari,1 Jiro Terada,1 Koichiro Tatsumi1 1Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba city, Chiba 260-8670, Japan; 2Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Narita city, Chiba 286-8686, Japan Introduction: The INPULSIS-ON trial demonstrated that nintedanib reduced decline in forced vital capacity (FVC) and low pulmonary function (%FVC < 50%) of patients with idiopathic pulmonary fibrosis (IPF). However, there is no sufficient evidence in real world.Objectives: Reveal the utility and adverse events of nintedanib for severe IPF patients.Methods: This was a single-center retrospective study. Patients who met the eligibility criteria of the INPULSIS trial (%FVC ≥ 50%; %DLCO [diffusing capacity of the lung carbon monoxide % predicted] ≥ 30%) were classified as Mild to Moderate Group (n = 34); patients who did not meet the criteria were classified as Severe Group (n=17).Results: The body mass index (24.7 ± 3.4 vs 22.4 ± 3.6 kg/m2; P = 0.021) were significantly low in Severe Group. Main adverse events (diarrhea, nausea, liver disorder, and acute exacerbation) tended to be more in Severe Group than in Mild to Moderate Group; however, the difference was not significant (P = 0.76, 0.14, 0.18, and 0.67, respectively). The continuation rates over 12 months tended to be higher in Mild to Moderate Group than in Severe Group (77% vs 44%; P = 0.027). Log-rank test revealed that the prognosis was significantly better in Mild to Moderate Group than in Severe Group (P = 0.014). In the Severe Group, patients who were able to continue nintedanib for more than 3 months had significantly better prognosis compared to those who could not (P = 0.007).Conclusion: The benefit from nintedanib was reduced in patients in Severe Group when compared to those in Mild to Moderate Group; however, the prognosis is expected to improve with control of side effects and long-term administration. It is more important to control the side effects in Severe Group. Keywords: idiopathic pulmonary fibrosis, nintedanib, triple tyrosine kinase inhibitor, INPULSIS trials, forced vital capacity

Abstract Background We hypothesise, based upon the findings from our previous trial, that the addition of co-trimoxazole to standard therapy is beneficial to patients with moderate to severe idiopathic pulmonary fibrosis (IPF). We aim to investigate this by assessing unplanned hospitalisation-free survival (defined as time from randomisation to first non-elective hospitalisation, lung transplant or death) and to determine whether any effect relates to changes in infection and/or markers of disease control and neutrophil activity. Methods/design The EME-TIPAC trial is a double-blind, placebo-controlled, randomised, multicentre clinical trial. A total of 330 symptomatic patients, aged 40 years old or older, with IPF diagnosed by a multidisciplinary team (MDT) according to international guidelines and a FVC ≤ 75% predicted will be enrolled. Patients are randomised equally to receive either two tablets of co-trimoxazole 480 mg or two placebo tablets twice daily over a median treatment period of 27 (range 12–42) months. All patients receive folic acid 5 mg daily whilst on the trial IMP to reduce the risk of bone marrow depression. The primary outcome for the trial is a composite endpoint consisting of the time to death, transplant or first non-elective hospital admission and will be determined from adverse event reporting, hospital databases and the Office of National Statistics with active tracing of patients missing appointments. Secondary outcomes include the individual components of the primary outcome, (1) King’s Brief Interstitial Lung Disease Questionnaire, (2) MRC Dyspnoea Score, (3) EQ5D, (4) spirometry, (5) total lung-diffusing capacity and (6) routine sputum microbiology. Blood will be taken for cell count, biochemistry and analysis of biomarkers including C-reactive protein and markers of disease. The trial will last for 4 years. Recruitment will take place in a network of approximately 40 sites throughout the UK (see Table 1 for a full list of participating sites). We expect recruitment for 30 months, follow-up for 12 months and trial analysis and reporting to take 4 months. Discussion The trial is designed to test the hypothesis that treating IPF patients with co-trimoxazole will increase the time to death (all causes), lung transplant or first non-elective hospital admission compared to standard care (https://www.nice.org.uk/guidance/cg163), in patients with moderate to severe disease. The mechanistic aims are to investigate the effect on lung microbiota and other measures of infection, markers of epithelial injury and markers of neutrophil activity. Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 17464641. Registered on 29 January 2015.

Background: Chronic hypersensitivity pneumonitis (HP) is the most common cause of diffuse parenchymal lung disease (DPLD) in India. There is no data regarding the avian antigen exposure-associated DPLD from the country. Methods: Chronic HP from exposure to avian antigen was diagnosed when the high resolution computerized tomography (HRCT) showed features for HP and was supported by the history of exposure to pigeons, the presence of precipitin antibodies (IgG) to avian antigen in high titre with negative rheumatoid factor, antinuclear antibody, and no clinical clue for a collagen vascular disease. The HRCT changes were noted on Likert scale (0–5) in terms of affection of peripheral and/or axial involvement, reticulation, honeycombing, haze, mosaic, traction bronchiectasis, pleural reactions, features of pulmonary hypertension, and air cysts. Cardiomegaly and independent cardiac chamber enlargement were also recorded. Results: The lower lobes were predominantly (65.6%) affected with similar frequency (78.1) of peripheral and axial parenchymal affection. The parenchymal changes in HRCT were haze or ground-glass opacity (100%), mosaic appearance (93.75%), reticulations (68.75%), traction bronchiectasis (34.3%), air cysts (21.8%), and honeycombing (9.37%). Pleural reactions, though not described so far, were found in 50% of cases. Features of pulmonary hypertension (87.5%), cardiomegaly (50%), left and right atrial enlargement (81.2% and 78.1%), and right ventricular enlargement (31.2%) were the common echocardiography findings. Conclusion: Chronic HP from avian exposure shows predominantly lower lobe involvement with haze, reticulation, features of pulmonary hypertension, and pleural reactions as common HRCT findings. The likelihood of pulmonary hypertension appears high and although honeycombing is often present, the classical UIP pattern has not been found.

Cervical epidural anesthesia for breast surgery has been described in a few trials on patients with good physical status. This case report describes the successful use of cervical epidural anesthesia in a patient with severe respiratory compromise without any complication. A 72-year-old female patient having infiltrating duct carcinoma of the right breast with coexisting chronic obstructive airway disease and bronchial asthma was planned for modified radical mastectomy with axillary clearance. Her forced vital capacity (VC) was 28% predicted with reversibility of 24% and forced expiratory volume in 1 s was 31% predicted with 35% reversibility. After discussion with the surgical team, a regional anesthetic was planned for the patient and a cervical epidural catheter placed at C7–T1 interspace was used to provide adequate dermatomal anesthesia for the surgery. Dexmedetomidine was used to achieve sedation for patient comfort with minimal respiratory depression. The SpO2 and end-tidal CO2 recordings remained stable throughout the procedure, with excellent intra- and postoperative analgesia. Despite the concerns of bilateral phrenic nerve palsy with the use of cervical epidural anesthesia and associated decrease in VC, a carefully conducted cervical epidural anesthesia can be used for patients with respiratory compromise undergoing major breast surgery. Radical mastectomy, cervical epidural anesthesia, low FEV1, FVC, dexmedetomidine.

The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) varies among individuals. Red blood cell distribution width (RDW) has been reported to be a predictor of idiopathic pulmonary fibrosis. However, there are no studies on the relationship between RDW and SSc-ILD. We conducted a retrospective study of 28 patients who were diagnosed with SSc-ILD on their first visit to our hospital and were followed-up for 5 years. The correlation between the changes in RDW, KL-6, and SP-D (ΔRDW, ΔKL-6, ΔSP-D) and the changes in percent-predicted forced lung volume and % carbon monoxide diffusion (Δ%FVC, Δ%DLco) was investigated. ΔRDW at 1 year after diagnosis was significantly inversely correlated with Δ%FVC at 5 years after diagnosis (r = −0.51, p < 0.001) and Δ%DLco at 5 years after diagnosis (r = −0.47, p < 0.001), whereas ΔKL-6 and ΔSP-D at 1 year were not correlated with Δ%FVC or Δ%DLco at 5 years. In the group of SSc-ILD patients with RDW increase in the first year after diagnosis, %FVC and %DLco were significantly lower than baseline at 3-, 4-, and 5-year assessments. In the group of patients without RDW increase in the first year, %FVC and %DLco did not decrease during the follow-up period. In conclusion, the changes in RDW in the first year after diagnosis may be useful surrogate markers to predict the long-term course of SSc-ILD.

Introduction: Water-based exercises are widely accepted exercises due to its acceptance and additional benefits from them. Exclusively, aquatic exercises are more advantageous than Land Exercises (LE), particularly in the early phase after rehabilitation for respiratory benefits. Aim: To evaluate the efficacy of water-based inspiratory muscle training in respiratory muscle strength, lung functions and functional capacity in patients with Parkinson's Disease (PD). Materials and Methods: A longitudinal study was conducted on 30 participants with idiopathic PD, at Chandigarh University, Mohali, Punjab, India, between 50-65 years and in stages I-III (Modified Hoehn and Yahr Scale). Respiratory muscle strength was evaluated through inspiratory muscle training and functional capacity was evaluated with a 6-minute walk test. After the assessment, the participants were randomly assigned into two groups. Group A: Along with conventional exercise, waterbased inspiratory muscle training was given to the population of this group. Group B: Along with conventional exercise, landbased respiratory muscle training was given to the population of this group. Results: Mean age of group A was 69±6 years and group B was 69±4 years (p-value=0.90). As per statistical analysis using paired t-test, both the groups showed improvement from baseline in all the parameters {Forced Vital Capacity (FVC)%, Forced Expiratory Volume in one second (FEV1)%, Maximal Expiratory Pressure (MEP) (cmH2O)} after the intervention. When compared within the groups using independent sample t-test, there was statistically significant change seen in mean value of the parameters and group A was found to be better as compared to Group B. Conclusion: The study revealed that water-based respiratory muscle training is safe and more effective intervention as compared to land-based exercise. Further, water-based intervention safely helps in improvement of inspiratory and expiratory muscle strength, pulmonary functions as well as for general body activity in patients with mild-to-moderate PD. [ABSTRACT FROM AUTHOR]