Improvement In Pulmonary Function Tests Research Articles

Assessment of hyaluronic acid in COPD patients as a prognostic biomarker

BackgroundOne essential element of the extracellular matrix is hyaluronic acid (HA). It has been claimed that HA and its metabolism are different in the lungs of patients with chronic obstructive pulmonary disease (COPD). The present study investigated the predictive significance of serum level of HA in patients with COPD and monitored changes in its level in these patients because of therapy.MethodsHA was assessed in 60 patients with stable COPD (divided into subgroups I and II) and 20 healthy controls and then repeated after 3 and 6 months in COPD patients.ResultsMost of the patients were males (63.3%), and their ages ranged from 30 to 90. The serum level of HA was significantly increased in subgroups I and II (269.33 ± 4, 290 ± 4, respectively), compared to the control group (147.5 ± 1) with a significant difference in its level between both (p < 0.0001). The serum level of HA was significantly decreased in both subgroups 3 and 6 months later following adjustment of treatment and associated with improvement in pulmonary function test. There were significant positive correlations between HA and age as well as smoking index. Its level correlated negatively with forced expiratory volume in the first second (FEV1%), forced vital capacity (FVC%), and FEV1/FVC.ConclusionsHA is a useful marker for identifying clinical stability in COPD patients and for follow-up in the efficacy of treatment.

Antioxidant effect of vitamin C on asthmatic patients

Objective: To investigate the effect of vitamin C supplementation in decreasing asthma severity, medications, and improving pulmonary function tests (PFTs). Methodology: Search of electronic databases was conducted to identify relevant studies published from January 2010 up to November 2023. A total of 105 records were initially identified. After filtering and screening, just 9 studies met the inclusion criteria; 3 were reviews, while the remaining 6 were original. Of the original studies, one was experimental, performed on 24 male Balb/c mice while the remaining 5 were performed on 969 asthmatic patients. Except for the experimental study, the selected studies were performed in different settings and on different ethnicities at the age of seven years and over. Results: The results showed antioxidant effects of vitamin C in asthmatic patients and experimental models. The studies showed that vitamin-C supplements significantly contributed to the reduction in asthma severity, number of attacks, admission rate, and asthma medications. Also, improvement of PFTs and suppression of asthma phenotype features in asthma mouse models. Only one review showed non-significant improvement in symptoms and PFTs, with significant improvement in malondialdehyde level and superoxide dismutase activity. Conclusion: Vitamin C supplementation to asthmatic patients showed improvements in asthma symptoms and PFTs, decreases the dose of asthma medications through potentiation of their efficacy, and less reactive response in asthma mouse model.

Outcomes of bronchoscopic lung volume reduction coil treatment in patients with severe emphysema

Background: This study aims to evaluate the outcomes of bronchoscopic lung volume reduction coil treatment in patients with severe emphysema. Methods: Between February 2016 and March 2019, a total of 20 severe emphysema patients (19 males, 1 female; mean age: 65.2±5.2 years; range, 52 to 73 years) who underwent bronchoscopic lung volume reduction coil treatment were included. Each patient underwent pre- and post-treatment (6 and 12 months) pulmonary function tests, 6-min walking distance, modified Medical Research Council dyspnea scores, and diffusing capacity of the lung for carbon monoxide tests. Results: An mean number of 12.0±3.8 coils was placed in each lobe. There were significant improvements in the patients' pulmonary function tests and quality of life 12 months after the treatment. There was a significant difference in dyspnea as assessed by the modified Medical Research Council dyspnea scores 12 months after treatment compared to pre-treatment scores (p&lt;0.05). There was no change in the pulmonary function tests six months after treatment, while a significant improvement was seen at 12 months (p&lt;0.05). Conclusion: Bronchoscopic lung volume reduction coil treatment seems to be a promising modality for severe emphysema patients with significant improvements in the pulmonary function test results, modified Medical Research Council dyspnea scores, and 6-min walking distance.

Halo-gravity traction combined with growing rod treatment: an effective preoperative management for severe early-onset scoliosis.

The aim of this study was to investigate the effectiveness of preoperative halo-gravity traction (HGT) with subsequent growing rod (GR) treatment in patients with severe early-onset scoliosis (EOS). The authors retrospectively reviewed a cohort of patients with severe EOS who had received preoperative HGT with subsequent GR treatment at their center between January 2008 and January 2020. Patients with a Cobb angle in the coronal or sagittal plane that was > 90° were included. All patients received at least 6 weeks of HGT before GR placement. Results of pulmonary function tests (PFTs) and blood gas tests were compared before and after HGT. Radiological parameters were compared pre-HGT, post-HGT, postindex surgery, and at the latest follow-up. A total of 28 patients (17 boys and 11 girls, mean age 6.1 ± 2.3 years) were included in this study. After a mean of 65.2 ± 22.9 days of traction, the Cobb angle decreased from 101.4° ± 12.5° to 74.5° ± 19.3° (change rate 26.5%), and the kyphosis angle decreased from 71.1° ± 21.2° to 42.7° ± 9.5° (change rate 39.9%). There was a significant improvement in BMI but a decrease in hemoglobin levels following HGT. No HGT-related complications were recorded except pin site infections in 2 patients. Statistically significant improvements in PFTs after HGT were observed in forced vital capacity (FVC) (p = 0.011), the percentage predicted FVC (p = 0.007), FEV1 (p = 0.015), and the percentage predicted forced expiratory volume in 1 second (FEV1) (p = 0.005). Fourteen patients received assisted ventilation due to preoperative hypoxia, alveolar hypoventilation, or hypercapnia. Significant improvement was seen in PaCO2 (p = 0.008), PaO2 (p = 0.005), actual bicarbonate (p = 0.005), and oxygen saturation (p = 0.012) in these patients. After the index surgery, the Cobb angle decreased to 49.5° ± 18.9° and the kyphosis angle decreased to 36.2° ± 25.8°. After a mean of 4.3 ± 1.4 lengthening procedures, the Cobb angle was 56.5° ± 15.8°, and the kyphosis angle was 38.8° ± 19.7°. Surgical complications occurred in 14 (50%) patients, but none of these patients required revision surgery at the latest follow-up. Preoperative HGT notably improved both spinal deformity and pulmonary function in patients with severe EOS. GR treatment after HGT is a safe and effective strategy for these patients.

Using the 6-min walk test to assess the clinical response to mepolizumab and conventional therapy in severe eosinophilic asthma.

Severe asthma limits exercise to avoid respiratory symptoms. The objective of the present study was to investigate the role of the 6-min walk test (6MWT) in severe asthma. Consecutive patients with severe eosinophilic asthma were enrolled. A 6MWT was performed before and after 12 months. Inhaled therapy dose, oral corticosteroids dose, pulmonary function tests, eosinophil blood count, fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) score and responses to the Asthma Quality of Life Questionnaire (AQLQ) were also recorded. Of the 22 patients enrolled, 13 were treated with mepolizumab 100 mg every 4 weeks in addition to conventional therapy and nine with conventional therapy only. The majority of the patients were treated with high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists, while approximately half were on continuous oral corticosteroids. After 12 months, the mepolizumab group only showed a significant improvement in pulmonary function tests (percentage forced expiratory volume in 1 s and percentage forced expiratory flow at 25-75% forced vital capacity (FEF25-75%), both p<0.001; percentage forced vital capacity, p<0.01) and clinical laboratory parameters (eosinophil count, FeNO measured at a flow rate of 50 mL·s-1, ACT and AQLQ, p<0.001). No significant changes in the proportion of patients using continuous oral corticosteroids and high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists were observed in either group (p>0.05). By paired comparisons, statistically significant improvements of the mean 6-min walk distance (6MWD) were observed in the mepolizumab (p<0.001) and conventional therapy (p<0.01) groups, while no improvement was seen in dyspnoea Borg scale, heart rate, percentage oxygen saturation or systolic and diastolic blood pressure. 6MWD showed significant direct correlations with ACT (r=0.5998, p<0.001), AQLQ (r=0.3978, p=0.009) and FEF25-75% (r=0.3589, p=0.017). The 6MWT could complement severe asthma assessment and be relevant in evaluating the objective response to treatment, including biological therapies like mepolizumab.

Pulmonary Functional Outcomes at 3 Months in Critical COVID-19 Survivors Hospitalized during the First, Second, and Third Pandemic Waves.

Despite improved management of patients with COVID-19, we still ignore whether pharmacologic treatments and improved respiratory support have modified outcomes for intensive care unit (ICU) surviving patients of the three first consecutive waves (w) of the pandemic. The aim of this study was to evaluate whether developments in the management of ICU COVID-19 patients have positively impacted respiratory functional outcomes, quality of life (QoL), and chest CT scan patterns in ICU COVID-19 surviving patients at 3 months, according to pandemic waves. We prospectively included all patients admitted to the ICU of two university hospitals with acute respiratory distress syndrome (ARDS) related to COVID-19. Data related to hospitalization (disease severity, complications), demographics, and medical history were collected. Patients were assessed 3 months post-ICU discharge using a 6 min walking distance test (6MWT), a pulmonary function test (PFT), a respiratory muscle strength (RMS) test, a chest CT scan, and a Short Form 36 (SF-36) questionnaire. We included 84 ARDS COVID-19 surviving patients. Disease severity, complications, demographics, and comorbidities were similar between groups, but there were more women in wave 3 (w3). Length of stay at the hospital was shorter during w3 vs. during wave 1 (w1) (23.4 ± 14.2 days vs. 34.7 ± 20.8 days, p = 0.0304). Fewer patients required mechanical ventilation (MV) during the second wave (w2) vs. during w1 (33.3% vs. 63.9%, p = 0.0038). Assessment at 3 months after ICU discharge revealed that PFTs and 6MWTs scores were worse for w3 > w2 > w1. QoL (SF-36) deteriorated (vitality and mental health) more for patients in w1 vs. in w3 (64.7 ± 16.3 vs. 49.2 ± 23.2, p = 0.0169). Mechanical ventilation was associated with reduced forced expiratory volume (FEV1), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO), and respiratory muscle strength (RMS) (w1,2,3, p < 0.0500) on linear/logistic regression analysis. The use of glucocorticoids, as well as tocilizumab, was associated with improvements in the number of affected segments in chest CT, FEV1, TLC, and DLCO (p < 0.01). With better understanding and management of COVID-19, there was an improvement in PFT, 6MWT, and RMS in ICU survivors 3 months after ICU discharge, regardless of the pandemic wave during which they were hospitalized. However, immunomodulation and improved best practices for the management of COVID-19 do not appear to be sufficient to prevent significant morbidity in critically ill patients.

Administration of Δ8-tetrahydrocannabinol enhances lung function and attenuates neutrophiles infiltration in a preclinical model of acute respiratory distress syndrome

Abstract Acute respiratory distress syndrome ARDS, characterized by severe hypoxemia, is an inflammatory response leads to high mortality rate. Patients with ARDS, such as some COVID-19 patients, suffer from pulmonary alveolar damage and major oedema due to diffuse infiltration of immune cells. Neutrophils are predominantly elevated in the bronchoalveolar lavage fluids of ARDS patients. Our laboratory already reported that Δ9-tetrahydrocannabinol (THC) administration effectively attenuated lung inflammation, cytokine storm, and prevents mortality in ARDS. In current study, we tested the effect of Δ8-THC, a cannabinoid which is less psychoactive than Δ9-THC, in lipopolysaccharide-endotoxin (LPS)-induced model of ARDS. Our data showed that Δ8-THC exhibited improvement of pulmonary function tests and decreased bronchoconstriction index in freely conscious-tested animals accompanied with significant decreasing in immune cells infiltration, specifically neutrophiles, and decreasing of serum tumor necrosis factor alpha (TNFα) level. Interestingly, Single cell RNA sequencing analysis of pulmonary cell tSNE clusters showed that Δ8-THC dramatically reduced neutrophils clusters and dysregulates certain genes involved in movement of neutrophils and chemokines production such as CCl6, CCl9, Cxcl3, Cxcl10, and CCl5. Together, these findings suggest that Δ8-THC mitigates ARDS by preventing neutrophiles trafficking into the lungs, and thus, may serve as a therapeutic agent to treat ARDS. This work was supported in parts by NIH grants R01ES030144, P01AT003961, P20GM103641, and R01AI123947, R01AI160896

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

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

89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial

IntroductionImmune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment.MethodsTwenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder.ResultsFifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (K = 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06; P = 0.02).ConclusionRituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy.Trial registrationClinicaltrials.gov identifier NCT02251964

Modulation of Heart Rate Variability in Stressed Medical Students Via Breathing Exercise

Background: Stress in medical students is a global concern. Stress disturbs the sympathovagal balance and affects heart rate variability, a sign of healthy cardiovascular homeostasis. Various strategies have been used globally to combat stress and its effects. Aim: To determine how blowing balloon exercise modulatesheart rate variability (HRV) in stressed medical students. Methodology: A pretest-posttest quasi-experimental study wasconducted among stressed medical students at Islamic international medical college Rawalpindi Pakistan. Sixty students diagnosed with moderate stress were enrolled based on Depression Anxiety Stress Scale (DASS) Proforma. The study population was selected by simple random sampling via the balloting method among the stressed medical students. Study participants underwent a supervised blowing balloon exercise.Before and after a supervised blowing balloon exercise, the participants' pulmonary function tests, electrocardiograms, and DASS scores were measured. Participants' ECGs and pulmonary function tests were recorded viaPower lab (A.D. Instruments, model yam 4/25T, South Wales, Australia). Results: Blowing balloon exercise resulted in a significant reduction of DASS score (p&lt;0.001) and significant improvement in pulmonary function tests (p&lt;0.001). Among Heart rate variability parameters, the participants' standard deviation of successive N-N intervals, high-frequency components, and high-frequency normalized units significantly increased (p&lt;0.05) after blowing balloon exercise. Heart rate, low-frequency normalized units, and the ratio of low-frequency normalized value to high-frequency normalized value were significantly reduced (p&lt;0.05) after blowing balloon exercise. Conclusions: Blowing balloon exercise enhances medical students' heart rate variability and pulmonary function tests while reducing their stress levels. This cost-effective and easy exercise can be performed by stressed students without any time or place barrier. Keywords: Anxiety, Breathing Exercise, Depression, Heart Rate Variability, Stress, Sympathovagal Balance.

Retrospektivna procjena učinka nintedaniba u mišjem modelu plućne fibroze

Pulmonary function tests (PFTs) routinely implemented in clinics are the first step in the diagnosis of idiopathic pulmonary fibrosis. Evaluation of PFTs in the mouse model of pulmonary fibrosis accompanied by histological readouts may improve the clinical predictability of new therapeutic candidates. Forced vital capacity (FVC) is considered the most predictive of restrictive pulmonary disorders. This study aimed to test the improvement of PFT in mice lung fibrosis induced by treatment with an approved substance nintedanib, considered the gold standard. The hypothesis that treatment in animal models will demonstrate similar effects as in humans in the most relevant clinical outcomes was tested. Two experimental designs were enrolled in this study, a preventive regimen, with treatment initiation from the day of the challenge; and a therapeutic regimen, starting on day 7 postchallenge when fibrotic changes are present in the lungs. Experiments were terminated at two different time points, at 14 and 21 days postchallenge. C57BL/6 mice were administered with bleomycin (BLM) intranasally and treated with nintedanib from day 0 to day 14 or from day 7 until day 21. Fourteen or 21 days after the BLM challenge, PFTs were assessed using the in vivo invasive lung function measurement system Buxco® Pulmonary Function Test (PFT) (DSI™, New Brighton, USA). Histological evaluation was performed as a modified Ashcroft score. The bleomycin challenge induced a significant decrease of FVC in both experiments. However, nintedanib treatment given in both regimens significantly improved lung functionality. These findings were confirmed with histological analysis of the Ashcroft scoring system, modified by Matsuse. In conclusion, a good correlation between functional test parameters and the clinical effect of nintedanib was shown in both experiments: the preventive regimen was sampled 14 days post-challenge and the therapeutic regimen 21 days post-challenge. Based on these findings, the implementation of PFTs could be a good platform to increase the translational value of the model and potential new treatments.

Role of Bambuterol in the Management of Bronchial Asthma

Background: Asthma is a long-term inflammatory disorder of the airways characterized by wheezing, dyspnea, and cough. For the last few decades, inhalational devices have been used in the management of the disease, but compliance remains the problem. Higher doses of oral medications used with prominent side effects precluded the use of oral beta-agonist bronchodilators, and the search for an ideal beta-adrenergic bronchodilator continues. This study was conducted for evaluation of the role of oral bambuterol in the management of bronchial asthma. Aims and Objectives: Our study aimed to evaluate the potency and effectiveness of oral bambuterol in the management of the disease in fifty patients followed up over 2 weeks with objective assessment of symptom scores and changes in the frequency of rescue bronchodilator after 2 weeks of treatment. Side effects, if any, were documented for all patients. Methods: The study was conducted on fifty patients with chronic bronchial asthma. They were given 10 mg of bambuterol once daily orally for 14 days. Pulmonary function tests were performed at days 1, 7, and 14. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow rate (PEFR) were measured. Patients were assessed for symptom score and side effects at days 1, 7, and 14. Results: After completion of the study, significant improvement in the symptom score, FVC, FEV1, and PEFR was obtained with minimal side effects. Conclusion: Bambuterol 10 mg oral tablet once a day provides significant improvement in pulmonary function tests and effectively reduces asthmatic symptoms with minimal side effects.

The impact of multistrains of probiotics on Th17-related cytokines in patients with asthma: a randomized, double-blind, placebo-controlled trial

Objective Asthma is known as one of the most common chronic inflammatory diseases characterized by recurrent obstruction and inflammation of the airways. Probiotics are defined as a group of beneficial living microorganisms that are beneficial in many disorders, including allergies. The aim of this study was to investigate the probiotic supplement effects on improvement of clinical asthma symptom and changes in the pattern of Th17-related inflammatory cytokines in asthmatic patients. Methods This was a randomized controlled clinical trial with parallel, double-blind groups. Forty patients with asthma were enrolled and received 1 capsule/day of a probiotic supplement for 8 weeks. Respiratory function tests; and the level of IL-6, IL-17, IL-21 and TGF-β were evaluated at the baseline and end of intervention. Results The results showed that the level of IL-6 and IL-17 in patients after receiving probiotics was reduced and expression of TGF-β was increased as compared to the baseline. Also, the expression of IL-17 and IL-21 in the probiotic group was significantly lower than the placebo group at the end of the intervention. In addition, an improvement in pulmonary function tests and clinical symptoms was observed after receiving probiotics. Conclusions Eight-weeks treatment with a probiotic supplementation suggests that it may effect on Th17 cells-associated IL-6, IL-17 and TGF-β; and Forced Expiratory Volume in 1 s and Forced Vital Capacity. Taken together, these results suggest that probiotics may have the ability to affect neutrophilic asthma and they can possibly be used besides common treatments for patients with neutrophilic asthma.

Laparoscopic fundoplication for para-oesophageal hernia repair improves respiratory function in patients with dyspnoea: a prospective cohort study.

BackgroundDyspnoea in patients with a para-oesophageal hernia (PEH) occurs in 7% to 32% of cases and is very disabling, especially in elderly patients, and its origin is not well defined. The present study aims to assess the impact of PEH repair on dyspnoea and respiratory function.MethodsFrom January 2019 to May 2021, all consecutive patients scheduled for PEH repair presenting with a modified Medical Research Council (mMRC) score ≥ 2 for dyspnoea were included. Before and 2 months after surgery, dyspnoea was assessed by both the dyspnoea visual analogue scale (DVAS) and the mMRC scale, as well as pulmonary function tests (PFTs) by plethysmography.ResultsAll 43 patients that were included had pre- and postoperative dyspnoea assessments and PFTs. Median age was 70 years (range 63–73.5 years), 37 (86%) participants were women, median percentage of the intrathoracic stomach was 59.9% (range 44.2–83.0%), and median length of hospital stay was 3 days (range 3–4 days). After surgery, the DVAS decreased statistically significant (5.6 [4.7–6.7] vs. 3.0 [2.3–4.4], p < 0.001), and 37 (86%) patients had a clinically significant decrease in mMRC score. Absolute forced expiratory volume in one second (FEV1), total lung capacity, and forced vital capacity also statistically significantly increased after surgery by an average of 11.2% (SD 17.9), 5.0% (SD 13.9), and 10.7% (SD 14.6), respectively. Furthermore, from the subgroup analysis, it was identified that patients with a lower preoperative FEV1 were more likely to have improvement in it after surgery. No correlation was found between improvement in dyspnoea and FEV1. There was no correlation between the percentage of intrathoracic stomach and dyspnoea or improvement in PFT parameters.ConclusionPEH repair improves dyspnoea and FEV1 in a statistically significant manner in a population of patients presenting with dyspnoea. Patients with a low preoperative FEV1 are more likely to have improvement in it after surgery.

Treatment of severe Kaposiform lymphangiomatosis positive for NRAS mutation by MEK inhibition.

Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

Calcineurin inhibitors in systemic sclerosis - a systematic literature review.

Objective:To review treatment effectiveness and adverse events of calcineurin inhibitors (CNIs) such as cyclosporin A (CsA) and tacrolimus in patients with systemic sclerosis (SSc).Methods:A systematic literature search was performed on PubMed and Web of Science using the predefined keywords ‘systemic sclerosis’, scleroderma, cyclosporin*, and tacrolimus. Articles were eligible for inclusion, if SSc patients had been treated with CNIs and data on treatment effects were available.Results:This systematic literature review identified 37 papers (19 case reports, 15 case series, 2 controlled studies, and 1 retrospective study) including 134 SSc patients treated with CNIs. In 34 of 37 papers, CsA was used. An improvement of skin fibrosis was observed in 77 of 96 (80.2%) patients using a wide variety of outcome measures and dose regimes. Both controlled studies showed significant improvements, one using a historical control group and one using a no-treatment control group. Improvement in pulmonary function tests (PFTs) occurred in 67.9% (19/28) of the patients who had reduced PFTs at baseline. In 58 (43.3%) cases, adverse renal events were reported, of which 7 (5.2%) were severe such as scleroderma renal crisis (SRC), CsA-associated nephropathy, or death by renal insufficiency. Adverse events led to dose reduction, treatment interruption, or withdrawal in 39 of 134 (29.1%).Conclusion:In this systematic literature review, signals for potential effectiveness of CsA for skin and pulmonary fibrosis were found, but the evidence level of the identified studies was too low to allow robust conclusions. Randomized controlled double-blind trials are needed to conclude on the effectiveness of CNIs in SSc. Renal toxicity of CNIs was confirmed in this review and needs to be considered in the design of such studies.

To study the effect of yoga asana and pranayama on pulmonary function test in chronic obstructive pulmonary disease (copd) patients

Background: Pranayama is an integral part of yoga training. Pranayama is a regulated breathing practice that improves airway responsiveness. Yoga asana and pranayama have been shown to reduce resting respiratory rate and enhance vital capacity, maximum voluntary ventilation, breath-holding time, maximal inspiratory pressure, and expiratory pressure.Aim: This study aims to study the effect of yoga, asana, and pranayama on pulmonary function disease (chronic obstructive pulmonary disease [COPD]) patients.Materials and Methods: This was a prospective observational study which was conducted in the Department of Physiology in association with the Department of Respiratory Medicine Santosh Medical College and Hospital, Ghaziabad, Uttar Pradesh, with a sample size of 55 participants on stable patients diagnosed (COPD) with aged between 40 and 65 years of either sex. Written informed consent and approval from the institutional ethics committee were taken before starting the study. The paired t-test was used to compare the mean and standard deviation of the quantitative variables. When the P < 0.05, the results are statistically significant. To conduct statistical analysis, SPSS 20.0 was used.Results: We observed a statistically significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FVC/FEV1 ratio, and peak expiratory flow rate after 8 and 12 weeks of yoga training compared to the first visit (0 week) baseline before yoga training.Conclusion: The results of our study showed that the regular practice of yoga, asana, and pranayama for 45 min a day minimum of 3 days a week for 12 weeks showed improvement in pulmonary function tests of COPD patients. It was also concluded that yoga and asana along with pharmacological treatment for COPD patients showed improved breathing patterns and pulmonary function parameters. It was observed that yoga, asana, and pranayama had improved physical condition by reducing weight and body mass index which enhances pulmonary function.

Effects of Nutritional Interventions in Individuals with Chronic Obstructive Lung Disease: A Systematic Review of Randomized Controlled Trials.

BackgroundThe role of nutrition and dietary patterns has been widely investigated in cancer, cardiovascular disease, and diabetes, but there are limited data on nutritional impact on COPD. This systematic review (PROSPERO-reg. no: CRD42020172712) aimed to investigate the effect of nutritional interventions on pulmonary and physical function, inflammation, and health-related quality of life among individuals with COPD.MethodsSystematic searches were conducted in Medline, Embase, and Cochrane, resulting in 3861 references. Studies focusing exclusively on inpatient-stays, underweight or obese patients were excluded. Double screening, extraction and bias assessment were conducted. Bias was assessed according to the Cochrane risk of bias tool for randomized controlled trials. Thirteen randomized controlled trials with 916 participants were included.ResultsThese trials investigated effects of protein supplementation, beetroot juice, increased fruit and vegetable intake, black seed oil, Tualang honey, Chlorella vulgaris-extract, whey-peptide containing nutritional drink, and increased macronutrient intake. The durations of the interventions were from weeks to a few months, and only one with duration >1 year (investigating increased fruit/vegetable intake). The intervention increasing fruit/vegetables found improvement in pulmonary function tests. Some interventions observed effects on systemic inflammation, health-related quality of life and physical function, although with some mixed results. Five were classified as poor, five as fair, and three as good in terms of risk of bias and quality.ConclusionIncreasing intake of fruits and vegetables over prolonged periods might have positive effects on lung function in individuals with COPD. Some nutritional interventions also observed effects on systemic inflammation, health-related quality of life, and physical function, although with some mixed results. Many of the trials were underpowered, had high dropout rates, or had a high risk of bias. Further research should investigate effect of prolonged dietary interventions.

A Study of Pulmonary Function Tests in Patients with Chronic Rhinosinusitis Following Endoscopic Sinus Surgery.

Chronic inflammatory disorders of the upper airways are extremely prevalent and they have a major impact on public health.To assess the change in pulmonary function tests in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery pre operatively and post operatively.To evaluate the difference in mean of FEV1, FEV1%, FVC, FVC%, FEV1/FVC in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery.Prospective observational study.From July 2019 to September 2020 in Department of ENT and Head & Neck surgery, SMS Medical College, Jaipur.There was a significant improvement in the mean FEV1, FEV1%, FVC, and FVC% values post-surgically (p < 0.05). In our study, there was also a significant improvement in the FEV1/FVC value at one month postoperatively, reflecting the effect of FESS on relieving the symptomatic lower airway obstruction.Our study concludes that following Functional Endoscopic Sinus Surgery there is significant improvement in pulmonary function tests reflecting the improvement of asymptomatic lower airway disease in cases of chronic rhinosinusitis.

The Objective Effect of Breast Implant Removal and Capsulectomy on Pulmonary Function

Background: Breast Implant Illness after aesthetic breast augmentation remains a poorly-defined syndrome. Prior published studies have identified difficulty breathing as a symptom, but definitive improvement in breathing following breast implant removal remains understudied. We hypothesized that patients presenting with breathing symptoms attributed to breast implants would have objective improvement in pulmonary function tests after complete implant/capsule explantation. Methods: A retrospective study of all patients who underwent investigation for symptomatic breast implants by a single surgeon over 2 years was conducted. Paired T-tests were used to compare PFTs before and after surgery. Multivariate analyses and linear regression models were used to examine the impact of patient- and implant-related factors, including size and texture on PFT changes. Results: Sixty-nine patients met inclusion criteria. Forced vital capacity (mean pre: 3.67 ± 0.61 L versus post: 3.82 ± 0.55 L), forced expiratory volume (2.78 ± 0.44 L versus 2.89 ± 0.39 L), and peak expiratory flow rate (5.91 ± 1.43 L versus 6.56 ± 0.96 L) were significantly improved postoperatively (P = 0.004, 0.01, 0.0001, respectively). Textured implants were associated with a greater improvement in PFTs after their removal (P = 0.009). Implant size and capsular contracture, even when controlled relative to body mass index, were not independent predictors of improvement. Conclusions: This study demonstrates that patients presenting with symptomatic breast implants with pulmonary complaints had significant improvement in pulmonary function after complete implant/capsule explantation. Forced vital capacity, forced expiratory volume, and peak expiratory flow rate consistent with a restrictive pattern of ventilation reliably improved in this symptomatic cohort. Textured implants were a significant predictive variable for improvement in pulmonary function.