Chronic Obstructive Pulmonary Disease (COPD) is associated with increased inflammatory responses to noxious particles, which can be further enhanced during Acute Exacerbation of COPD (AECOPD). Considering the important immunoregulatory function of vitamin D, high prevalence of Vitamin D Deficiency (VDD) in COPD patients and a negative link between vitamin D levels and inflammatory biomarkers, suggests the seemingly interesting mechanism of vitamin D effects on inflammation resolution during the conventional treatment of AECOPD. The admitted AECOPD patients with VDD were recruited and randomly allocated to receive either 300,000 IU of intramuscular vitamin D ( = 35) or placebo ( = 35). Primary outcomes included inflammation resolution dynamics, which were assessed by monitoring the serum levels of IL-6, IL-8, and hs-CRP. Symptom recovery was evaluated based on the modified Medical Research Council (mMRC) dyspnea scale on the 1st and 6th days of admission. Secondary outcomes included the length of hospital stay (LOS) and 30-day mortality rates. Inflammatory biomarkers were highest at Day 1. Baseline vitamin D levels were 11.25 ± 3.09 and 10.59 ± 3.90 ng/ml ( = 0.45), which reached 11.35 ± 3.16 and 18.17 ± 4.24 by Day 6 ( < 0.001) in the placebo and, vitamin-D groups, respectively. IL-6 levels significantly decreased in the vitamin-D vs. placebo group on the 6 day ( = 0.02); however, no significant differences were observed in IL-8 ( = 0.15) and hs-CRP ( = 0.24) levels, mMRC scale ( = 0.45), LOS ( = 0.20), and mortality rates ( = 0.61). Vitamin D replacement as adjunctive therapy may accelerate inflammation resolution in hospitalized AECOPD patients. Further studies were needed to establish vitamin D exact role on inflammation resolution in AECOPD.

SARS-CoV-2 pneumonitis can quickly strike to incapacitate the lung, leading to severe disease and sometimes death. In this perspective, we suggest that vitamin D deficiency and the failure to activate the vitamin D receptor (VDR) can aggravate this respiratory syndrome by igniting a wounding response in stellate cells of the lung. The FDA-approved injectable vitamin D analog, paricalcitol, suppresses stellate cell-derived murine hepatic and pancreatic pro-inflammatory and pro-fibrotic changes. Therefore, we suggest a possible parallel program in the pulmonary stellate cells of COVID-19 patients and propose repurposing paricalcitol infusion therapy to restrain the COVID-19 cytokine storm. This proposed therapy could prove important to people of color who have higher COVID-19 mortality rates and lower vitamin D levels.

In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.

BACKGROUND:Fatigue is a distressing symptom in patients with COPD. Little is known about the factors that contribute to fatigue in COPD. This review summarises existing knowledge on the prevalence of fatigue, factors related to fatigue and the instruments most commonly used to assess fatigue in COPD. METHODS:Pubmed, PsycINFO, EMBASE, Cochrane and CINAHL databases were searched for studies from inception up to 7 January 2020 using the medical subject headings "COPD" and "Fatigue". Studies were reviewed in accordance with PRISMA guidelines. RESULTS:196 studies were evaluated. The prevalence of fatigue ranged from 17-95%. Age (r=-0.23 to r=0.27), sex (r=0.11), marital status (r=-0.096), dyspnoea (r=0.13 to r=0.78), forced expiatory volume in 1 s % predicted (r=-0.55 to r=-0.076), number of exacerbations (r=0.27 to r=0.38), number of comorbidities (r=0.10), number of medications (r=0.35), anxiety (r=0.36 to r=0.61), depression (r=0.41 to r=0.66), muscle strength (r=-0.78 to r=-0.45), functional capacity (r=-0.77 to r=-0.14) and quality of life (r=0.48 to r=0.77) showed significant associations with fatigue. CONCLUSIONS:Fatigue is a prevalent symptom in patients with COPD. Multiple physical and psychological factors seem to be associated with fatigue Future studies are needed to evaluate these underlying factors in integral analyses in samples of patients with COPD.

Chronic exposure to environmental pollutants is a major contributor to the development and progression of obstructive airway diseases, including asthma and COPD. Understanding the mechanisms underlying the development of obstructive lung diseases upon exposure to inhaled pollutants will lead to novel insights into the pathogenesis, prevention and treatment of these diseases. The respiratory epithelial lining forms a robust physicochemical barrier protecting the body from inhaled toxic particles and pathogens. Inhalation of airborne particles and gases may impair airway epithelial barrier function and subsequently lead to exaggerated inflammatory responses and airway remodelling, which are key features of asthma and COPD. In addition, air pollutant-induced airway epithelial barrier dysfunction may increase susceptibility to respiratory infections, thereby increasing the risk of exacerbations and thus triggering further inflammation. In this review, we discuss the molecular and immunological mechanisms involved in physical barrier disruption induced by major airborne pollutants and outline their implications in the pathogenesis of asthma and COPD. We further discuss the link between these pollutants and changes in the lung microbiome as a potential factor for aggravating airway diseases. Understanding these mechanisms may lead to identification of novel targets for therapeutic intervention to restore airway epithelial integrity in asthma and COPD.

Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.

Studies have pointed out that air pollution may be a contributing factor to the coronavirus disease 2019 (COVID-19) pandemic. However, the specific links between air pollution and severe acute respiratory syndrome-coronavirus-2 infection remain unclear. Here we provide evidence from , animal and human studies from the existing literature. Epidemiological investigations have related various air pollutants to COVID-19 morbidity and mortality at the population level, however, those studies suffer from several limitations. Air pollution may be linked to an increase in COVID-19 severity and lethality through its impact on chronic diseases, such as cardiopulmonary diseases and diabetes. Experimental studies have shown that exposure to air pollution leads to a decreased immune response, thus facilitating viral penetration and replication. Viruses may persist in air through complex interactions with particles and gases depending on: 1) chemical composition; 2) electric charges of particles; and 3) meteorological conditions such as relative humidity, ultraviolet (UV) radiation and temperature. In addition, by reducing UV radiation, air pollutants may promote viral persistence in air and reduce vitamin D synthesis. Further epidemiological studies are needed to better estimate the impact of air pollution on COVID-19. and studies are also strongly needed, in particular to more precisely explore the particle-virus interaction in air.

BACKGROUND:The characteristics of optimal virtual pulmonary rehabilitation (PR) for individuals with post-COVID syndrome (PCS) have not been identified. This study aimed to assess the feasibility, safety, and satisfaction associated with a virtual PR program with the exercise component delivered through group or self-directed sessions. METHODS:Adults with PCS-respiratory symptoms were randomly assigned to the video conference (PR) or self-directed (PR) group and completed an exercise program (aerobic, strengthening, and breathing exercises) three times/week for eight weeks. PR sessions were led by a physiotherapist via Zoom, whereas the PR group exercised individually following a pre-recorded video. Both groups received personalized exercise recommendations, education related to the condition, and a weekly follow up call. Satisfaction was assessed through a patient survey. Lung function, dyspnea, fatigue, sit-to-stand capacity, health-related quality of life, and participation were assessed pre- and post-PR. RESULTS:Fourteen PCS individuals (49 ± 9 years, 86% females) completed 83% of the sessions. All participants were satisfied with information provided by the therapist and frequency of data submission, whereas most were satisfied with the frequency and duration of exercise sessions (88% in PR and 83% in PR). A higher proportion of participants in the PR (88%) were satisfied with the level of difficulty of exercises compared with the PR (67%), and 84% of the sample reported a positive impact of the program on their health. No adverse events were reported. Significant changes in sit-to-stand capacity (p = 0.012, Cohen's r = 0.67) and questions related to fatigue (p = 0.027, Cohen's r = 0.58), neurocognitive (p = 0.045, Cohen's r = 0.53), and autonomic (p = 0.024, Cohen's r = 0.60) domains of the DePaul Symptom Questionnaire short-form were also found between groups. CONCLUSION:Virtual PR with exercises delivered via video conference or pre-recorded video were feasible, safe, and well-received by individuals with PCS. TRIAL REGISTRATION:NCT05003271 (first posted: 12/08/2021).

BACKGROUND:Dyspnea, fatigue, and decline in sleep quality are symptoms of chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation programs have been shown to ameliorate dyspnea and fatigue. However, only a few studies have investigated the effects of pulmonary rehabilitation on the sleep quality of COPD patients. In this study, we analyzed the benefits of a pulmonary rehabilitation program to sleep quality and daytime somnolence in COPD patients. METHODS:This study was a study of 30 moderate-severe COPD patients. All patients were evaluated by a pulmonologist and underwent polysomnography before participating in the study. For this study, we selected only ex-smokers and patients with sleep apnea were referred to the sleep clinic. These participants were prospectively recruited and not selected based on program completion. Before the start of the program, sleep quality and daytime somnolence of the participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Rehabilitation program consisted of muscular training sessions conducted at the gym 3 times per week for 12 weeks. After rehabilitation program, the patients were reassessed and their sleep quality and daytime somnolence were reevaluated using the PSQI and the ESS, respectively. RESULTS:Before rehabilitation, PSQI evaluation revealed that 73% of the participants had poor sleep quality, and ESS evaluation showed that 86.7% of the participants experienced daytime somnolence. After pulmonary rehabilitation, the PSQI specifically improved in terms of subjective sleep quality and sleep duration (< 0.001), habitual sleep efficiency (0.001), and sleep latency and sleep alterations (0.002) and there was also improvement in the ESS (< 0.001). CONCLUSION:Pulmonary rehabilitation program of gradually increasing intensity has the potential to provide sleep-related benefits to patients with COPD who have poor sleep quality and daytime somnolence. TRIAL REGISTRATION:Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR62b4z2.

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a high symptom burden and poor survival that influences patients' health-related quality of life (HRQOL). We aimed to evaluate IPF patients' symptoms and HRQOL in a well-documented clinical cohort during their last two years of life. METHODS:In April 2015, we sent the Modified Medical Research Council Dyspnea Scale (MMRC), the modified Edmonton Symptom Assessment Scale (ESAS) and a self-rating HRQOL questionnaire (RAND-36) to 300 IPF patients, of which 247 (82%) responded. Thereafter, follow-up questionnaires were sent every six months for two years. RESULTS:Ninety-two patients died by August 2017. Among these patients, HRQOL was found to be considerably low already two years before death. The most prominent declines in HRQOL occurred in physical function, vitality, emotional role and social functioning (p < 0.001). The proportion of patients with MMRC scores ≥3 increased near death. Breathlessness and fatigue were the most severe symptoms. Symptom severity for the following symptoms increased significantly and reached the highest mean scores during the last six months of life (numeric rating scale/standard deviation): breathlessness (7.1/2.8), tiredness (7.0/2.3), dry mouth (6.0/3.0), cough (5.8/2.9), and pain with movement (5.0/3.5). CONCLUSIONS:To our knowledge this is the first study demonstrating, that IPF patients experience remarkably low HRQOL already two years before death, especially regarding physical role. In addition, they suffer from severe breathlessness and fatigue. Furthermore, physical, social and emotional wellbeing deteriorate, and symptom burden increases near death. Regular symptom and HRQOL measurements are essential to assess palliative care needs in patients with IPF.

BACKGROUND:Interstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease. METHODS:Eligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program. Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George's Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation. DISCUSSION:The standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease. Trial registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true.

BACKGROUND:Non-invasive ventilation (NIV) reduces respiratory load and demands on peripheral muscles. METHODS:This study aims to evaluate the acute effects of bi-level NIV on peripheral muscle function during isokinetic exercise and aerobic performance in chronic obstructive pulmonary disease (COPD) patients. This is a pilot crossover study performed with a non-probabilistic sample of 14 moderate to very severe COPD patients. Procedures carried out in two days. Dyspnea, quality of life, lung function, respiratory muscle strength, functional capacity (6-min walk test-6MWT), and isokinetic assessment of the quadriceps were assessed. Blood samples (lactate, lactate dehydrogenase, and creatine kinase concentration) were also collected. Right after, NIV was performed for 30 min (bi-level or placebo, according to randomization) followed by new blood sample collection, 6MWT, and isokinetic dynamometer tests. Before and after evaluations, the subjective perception of dyspnea and fatigue in the lower limbs was quantified. After a wash-out period of seven days, participants returned, and all assessments were performed again. RESULTS:NIV showed improvements in perceived exertion and dyspnea after isokinetic exercise (p < 0.02 and p < 0.05, respectively). CONCLUSIONS:NIV improves the perception of dyspnea and fatigue during the isokinetic exercise.

OBJECTIVE:To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. MATERIAL AND METHODS:Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. RESULTS:Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. CONCLUSION:Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

BACKGROUND:Asthma is the most common allergic disease characterized by an inflammatory response in the airways. Mechanismly, urban particulate matter (PM) is the most widely air pollutant associated with increased asthma morbidity and airway inflammation. Current research found that vitamin D is an essential vitamin with anti-inflammatory, antioxidant and other medical efficacy. Inadequate or deficient vitamin D often leads to the pathogenesis and stability of asthma. NGF exacerbates airway inflammation in asthma by promoting smooth muscle cell proliferation and inducing the Th2 immune response. Activation of the Nrf2/HO-1 signaling pathway can exert a protective effect on the inflammatory response in bronchial asthma. However, the specific mechanism of this pathway in PM-involved asthmatic airway smooth muscle cells remains unclear. METHODS:Mice were sensitized and challenged with Ovalbumin (OVA) to establish an asthma model. They were then exposed to either PM, vitamin D or a combination of both, and inflammatory responses were observed. Including, acetylcholine stimulation at different concentrations measured airway hyperresponsiveness in mice. Bronchoalveolar lavage fluid (BALF) and serum were collected for TNF-α, IL-1β, IL-6, and Nerve growth factor (NGF) analysis. Additionally, lung tissues underwent histopathological examination to observe alveolar structure and inflammatory cell infiltration. Specific ELISA kits were utilized to determine the levels of the inflammatory factors TNF-α, IL-1β, IL-6, and Nerve growth factor (NGF). Nrf2/HO-1 signaling pathways were examined by western blot analysis. Meanwhile, we constructed a cell system with low HO-1 expression by lentiviral transfection of airway smooth muscle cells. The changes of Nrf2, HO-1, and NGF were observed after the treatment of OVA, PM, and Vit D were given. RESULTS:The in vivo results showed that vitamin D significantly alleviated pathological changes in lung tissue of PM-exposed mice models. Mechanismly, vitamin D decreased substantial inflammatory cell infiltration in lung tissue, as well as the number of inflammatory cells in BALF. Furthermore, vitamin D reduced the heightened inflammatory factors including of TNF-α, IL-1β, IL-6, and NGF caused by PM exposure, and triggered the activity of nucleus Nrf2 and HO-1 in PM-exposed asthmatic mice. Notably, knockdown HO-1 weakens the Vitamin D- mediated inhibition to pollution toxicity in asthma. Importantly, in vitro experiments on OVA-stimulated mice airway smooth muscle cells, the results showed that OVA and PM, respectively, reduced Nrf2/HO-1 and increased NGF's expression, while vitamin D reversed the process. And in the HO-1 knockdown cell line of Lenti-si-HO-1 ASMCs, OVA and PM reduced Nrf2's expression, while HO-1 and NGF's expression were unchanged. CONCLUSIONS:The above results demastrate that vitamin D downregulated the inflammatory response and the expression of NGF by regulating the Nrf2/HO-1 signaling pathways in airway smooth muscle cells, thereby showing potent anti-inflammatory activity in asthma.

BACKGROUND:There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT). METHODS:Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made. RESULTS:Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69). CONCLUSIONS:Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.

BACKGROUND:Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes. METHODS:Current and former smokers between ages 45-80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire. RESULTS:Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans. CONCLUSION:Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes.

BACKGROUND:The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Polymorphisms in VDR or VDBP genes may affect vitamin D levels, influencing the pathogenesis of asthma and atopy. The aim of this study was to investigate the possible association of VDR and VDBP gene single-nucleotide polymorphisms (SNP), 25-hydroxyvitamin D (25(OH)D), blood eosinophils and total IgE level in subjects with asthma in comparison with healthy individuals. METHODS:This case-control study enrolled 63 subjects with asthma (45 allergic and 18 non-allergic) and 32 healthy subjects were involved in the study. Sensitization of subjects to inhaled allergens was determined by a skin prick test, lung function was evaluated by spirometry. Blood eosinophil count was determined by standard methods. Serum 25(OH)D and total IgE levels were evaluated by ELISA. Polymorphisms in the VDR and VDBP genes on the 12q13.11 and 4q13.3 chromosomal region were analyzed using TaqMan SNP Genotyping Assay probes. RESULTS:In asthma patients with vitamin D deficiency (< 20 ng/ml) the allele G of rs11168293 of VDR was more common than in those having insufficiency (20-30 ng/ml) of vitamin D (63% and 31%, p < 0.05). Moreover, asthmatic subject with rs11168293 G allele has significant higher blood eosinophil count compared to asthmatic without the rs11168293 G allele (8.5 ± 12.3% vs. 5.1 ± 1.5%, p < 0.05). Significantly higher IgE level was found in subjects with allergic asthma with the allele A of rs7041 on VDBP gene than in those without this allele (540 ± 110 and 240 ± 80 IU/ml, p < 0.05). CONCLUSIONS:The association of polymorphisms in VDBP and VDR gene, the rs11168293 G allele and the rs7041 A allele, with 25(OH)D, blood eosinophil and total IgE level in asthma, let us suggest that vitamin D, VDR and VDBP gene polymorphisms are important in pathogenesis of asthma despite its form in relation to atopy.

BACKGROUND:Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN:We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION:This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. TRIAL REGISTRATION:This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.