Common Chronic Lung Disease Research Articles

Rational inhalation therapy in COPD in India: Hope or hype!

Chronic obstructive pulmonary disease (COPD) is common chronic lung disease usually treated in all health care settings as per knowledge of disease, availability of medicines and affordability of patients in India. COPD is second leading cause of death in list of all cause of mortality. COPD is under evaluated and half-heartedly treated with irrational oral medicines in spite of rational inhalation therapy in primary to tertiary care settings. More than half of the cases died due to cardiovascular causes are having underlying COPD as precipitating factor. More disease awareness regarding use of spirometry in health care professionals for proper diagnosis of COPD with more emphasis on rational inhalation treatment is must to prevent morbidity of mortality of this treatable disease.

Protectin DX Relieve Hyperoxia-induced Lung Injury by Protecting Pulmonary Endothelial Glycocalyx.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants with limited treatments and poor prognosis. Damaged endothelial glycocalyx leads to vascular permeability, lung edema and inflammation. However, whether hyperoxia increases neonatal pulmonary microvascular permeability by degrading the endothelial glycocalyx remains unknown. Newborn mice were maintained in 60-70% O2 for 7 days. Protectin DX (PDX), an endogenous lipid mediator, was injected intraperitoneally on postnatal d 0, 2, 4 and 6. Lung samples and bronchoalveolar lavage fluid were taken at the end of the study. Primary human umbilical vein endothelial cells (HUVECs) were cultured in 80%O2. Hyperoxia exposure for 7 days led to neonatal mice alveolar simplification with less radial alveolar count (RAC), mean linear intercept (MLI) and mean alveolar diameter (MAD) compared to the control group. Hyperoxia exposure increased lung vascular permeability with more fluid and proteins and inflammatory factors, including TNF-α and IL-1β, in bronchoalveolar lavage fluid while reducing the heparan sulfate (HS), the most abundant component of the endothelial glycocalyx, in the pulmonary endothelial cells. PDX relieve these changes. PDX attenuated hyperoxia-induced high expression of heparanase (HPA), the endoglycosidase that shed endothelial glycocalyx, p-P65, P65, and low expression of SIRT1. BOC-2 and EX527 abolished the affection of PDX both in vivo and intro. In summary, our findings indicate that PDX treatment relieves hyperoxia-induced alveolar simplification, vascular leakage and lung inflammation by attenuating pulmonary endothelial glycocalyx injury via the SIRT1/NF-κB/ HPA pathway.

Pulmonary rehabilitation integrated coached exercise training for patients with COPD: a study protocol for a randomized controlled trial

BackgroundChronic obstructive pulmonary disease (COPD) is the most common chronic lung disease creating an immense burden on social health care systems. Pulmonary rehabilitation (PR) has proven to be effective in patients with COPD. However, exercise training as the basis of PR becomes extremely tedious, occasionally causing a loss of perseverance in patients. Therefore, we considered an approach that makes this technique interesting and easier to persist. The aim of this project was to explore an exercise training approach based on PR-integrated coached exercise training to promote the new exercise training approach as a form of group rehabilitation activity in the future.MethodsParticipants will be randomly divided into the trial and control groups. The trial group will be treated with PR-integrated coached exercise training (plus usual care). All exercise programs will be guided by sports coaches with a physical education background. Meanwhile, the control group will receive traditional PR and home exercises, including walking and swimming. The study will last for 12 weeks. The primary outcome measure is exercise tolerance using the 6-min walking test and secondary outcomes are the peak oxygen uptake of cardiopulmonary exercise tests, the COPD Assessment Test, and the St. Georges Respiratory Questionnaire. Other evaluated outcomes include changes in postbronchodilator forced expiratory volume at 1st second, forced vital capacity, body fat and muscle composition, and mental status measured using the Hamilton Anxiety and Depression Scales.DiscussionThis study provides a simple, feasible, repeatable, and fun exercise training approach. To the best of our knowledge, there are no randomized controlled trials in the existing literature on PR-integrated coached exercise. The protocol shared in our study can be used as a reference for exercise training in patients with COPD.Trial registrationEthical approval (BF2020-236–02) was obtained from the Guangdong Provincial Hospital of Chinese Medicine Human Research Ethics Committee. All participants signed an informed consent form. ChiCTR-2100043543. The registration date is 2021/02/21 and it is the third version.

Telerehabilitation and telemonitoring interventions programs used to improving quality of life in people with cystic fibrosis: A systematic review.

Cystic fibrosis causes mucus to build up in the lungs, digestive tract, and other areas. It is the most common chronic lung disease in children and young adults. It requires daily medical care. Before the COVID-19 pandemic, telerehabilitation and telehealth were used, but it was after this that there was a boom in these types of assistance in order to continue caring for cystic fibrosis patients. The objective is to evaluate the effect of telemedicine programs in people with cystic fibrosis. For the search, the PubMed, Scopus, Web of Science, PEDro, Cochrane, and CINAHL databases were used. Randomized controlled trials, pilot studies, and clinical trials have been included. The exclusion criteria have considered that the population did not have another active disease or that telemedicine was not used as the main intervention. This study follows the PRISMA statement and has been registered in the PROSPERO database (CRD42021257647). A total of 11 articles have been included in the systematic review. No improvements have been found in quality of life, forced expiratory volume, and forced vital capacity. Good results have been found in increasing physical activity and early detection of exacerbations. Adherence and satisfaction are very positive and promising. Despite not obtaining significant improvements in some of the variables, it should be noted that the adherence and satisfaction of both patients and workers reinforce the use of this type of care. Future studies are recommended in which to continue investigating this topic.

Obesity, Charlson comorbidity index, and neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease: relationship to disease severity.

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory lung disease with high mortality and morbidity rates. Obesity, various comorbid diseases, and inflammation often coexist in chronic obstructive pulmonary disease (COPD), exhibiting a complex interaction with disease severity. The aim of the study was to examine the relationship between COPD markers and obesity, the Charlson Comorbidity Index (CCI), and neutrophil/lymphocyte ratio (NLR). Eighty male patients with stable COPD admitted to the pulmonology unit were included in the study. The presence of comorbidities was investigated in obese and non-obese individuals with COPD. Pulmonary function tests and the mMRC dyspnea scale were examined, and CCI scores were calculated. 60.9 % with mild/moderate COPD, and 64.7 % with severe COPD had a comorbid disease. The incidence of hypertension and diabetes was significantly higher in obese patients. The obesity rate was 41.3 % in patients with mild/moderate COPD (FEV1 ≥ 50) and 26.5 % in those with severe COPD (FEV1 < 50). There was a positive and significant correlation between CCI value and BMI and mMRC dyspnea scale. NLR was significantly higher in patients with FEV1 < 50 and mMRC ≥ 2. As a result, it is essential to screen obese patients with COPD, who are among the groups with the highest incidence of comorbidities, in terms of such diseases that exacerbate the symptoms of their disease. Findings may support the potential applicability of simple blood count indices (such as NLR) in the clinical assessment of disease in stable COPD patients (Tab. 4, Fig. 1, Ref. 46).

Knockdown of FBLN2 suppresses TGF-β1-induced MRC-5 cell migration and fibrosis by downregulating VTN

Idiopathic pulmonary fibrosis (IPF) is a common chronic and progressive lung disease. Fibulin-2 (FBLN2) is upregulated in patients with IPF; however, its exact role in IPF remains unclear. The present study aimed to investigate the role and the regulatory mechanism of FBLN2 in TGF-β1-induced fibrogenesis using human lung fibroblast-derived MRC-5 cells. Cell transfection was performed to regulate FBLN2 expression. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of FBLN2 and vitronectin (VTN). Cell viability and migration were determined via the Cell Counting Kit-8 and wound healing assays, respectively. Immunofluorescence was performed to detect α-smooth muscle actin (α-SMA)-positive cells. The STRING database was used to predict the interaction between FBLN2 and VTN, which was verified via the protein immunoprecipitation assay. The results demonstrated that inhibition of FBLN2 notably inhibited TGF-β1-induced proliferation and migration, as well as downregulating the protein expression levels of MMP2 and MMP9 in MRC-5 cells. In addition, inhibition of FBLN2 suppressed the expression levels of α-SMA, collagen type 1 α1 and fibronectin. FBLN2 was demonstrated to bind to VTN and negatively regulate its expression. Furthermore, overexpression of VTN partly abolished the inhibitory effects of FBLN2 knockdown on TGF-β1-induced proliferation, migration and fibrosis, as well as the activity of focal adhesion kinase (FAK) signaling. Taken together, the results of the present study suggest that FBLN2 knockdown can attenuate TGF-β1-induced fibrosis in MRC-5 cells by downregulating VTN expression via FAK signaling. Thus, FBLN2 may be a potential therapeutic target for IPF treatment.

Bronchiectasis.

Bronchiectasis is a common chronic lung disease that is prevalent in the Australian community and is a significant disease burden in the Australian Aboriginal community. Itsignificantly affects quality of life andincreases healthcare costs; however, it ispoorly reported and documented. The aim of this article is to provide a comprehensive summary of the important features to recognise in bronchiectasis and an updated guide to the management of bronchiectasis. Bronchiectasis is an obstructive lung disease that is often associated with various underlying conditions that can occur as a result of infectious insult or impaired host defence. The main features of bronchiectasis are dilated airways with increased sputum production, recurrent exacerbations and impaired quality of life. Management is aimed at investigating and managing secondary causes with a focus on sputum clearance, reduction in exacerbations andimprovement of quality of life.

High-Resolution Computed Tomography of Nonfibrotic Interstitial Lung Disease.

Nonfibrotic interstitial lung diseases include a heterogeneous group of conditions that can result in various patterns of lung involvement. When approaching the computed tomographic (CT) scan of a patient with a suspected or known interstitial lung disease, the use of the appropriate radiological terms and a systematic, structured approach to the interpretation of the imaging findings are essential to reach a confident diagnosis or to limit the list of differentials to few possibilities. The large number of conditions that cause nonfibrotic interstitial lung diseases prevents a thorough discussion of all these entities. Therefore, this article will focus on the most common chronic lung diseases that can cause these CT findings. A pattern-based approach is used, with a discussion of nodular pattern, consolidation, crazy paving, ground-glass opacities, septal thickening, and calcifications. The different clinical conditions will be described based on their predominant pattern, with particular attention to findings that can help in the differential diagnosis.

Deficiency of endothelial FGFR1 alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice.

Disrupted neonatal lung angiogenesis and alveologenesis often give rise to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. Hyperoxia-induced pulmonary vascular and alveolar damage in premature infants is one of the most common and frequent factors contributing to BPD. The purpose of the present study was to explore the key molecules and the underlying mechanisms in hyperoxia-induced lung injury in neonatal mice and to provide a new strategy for the treatment of BPD. In this work, we reported that hyperoxia decreased the proportion of endothelial cells (ECs) in the lungs of neonatal mice. In hyperoxic lung ECs of neonatal mice, we detected upregulated fibroblast growth factor receptor 1 (FGFR1) expression, accompanied by upregulation of the classic downstream signaling pathway of activated FGFR1, including the ERK/MAPK signaling pathway and PI3K-Akt signaling pathway. Specific deletion of Fgfr1 in the ECs of neonatal mice protected the lungs from hyperoxia-induced lung injury, with improved angiogenesis, alveologenesis and respiratory metrics. Intriguingly, the increased Fgfr1 expression was mainly attributed to aerosol capillary endothelial (aCap) cells rather than general capillary endothelial (gCap) cells. Deletion of endothelial Fgfr1 increased the expression of gCap cell markers but decreased the expression of aCap cell markers. Additionally, inhibition of FGFR1 by an FGFR1 inhibitor improved alveologenesis and respiratory metrics. In summary, this study suggests that in neonatal mice, hyperoxia increases the expression of endothelial FGFR1 in lung ECs and that deficiency of endothelial Fgfr1 can ameliorate hyperoxia-induced BPD. These data suggest that FGFR1 may be a potential therapeutic target for BPD, which will provide a new strategy for the prevention and treatment of BPD.

Risk factors and machine learning prediction models for bronchopulmonary dysplasia severity in the Chinese population

BackgroundBronchopulmonary dysplasia (BPD) is a common chronic lung disease in extremely preterm neonates. The outcome and clinical burden vary dramatically according to severity. Although some prediction tools for BPD exist, they seldom pay attention to disease severity and are based on populations in developed countries. This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population.MethodsIn this retrospective, single-center study, we included patients with a gestational age < 32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020. We collected their clinical information during the maternal, birth and early postnatal periods. Risk factors were selected through univariable and ordinal logistic regression analyses. Prediction models based on logistic regression (LR), gradient boosting decision tree, XGBoost (XGB) and random forest (RF) models were implemented and assessed by the area under the receiver operating characteristic curve (AUC).ResultsWe ultimately included 471 patients (279 mild, 147 moderate, and 45 severe cases). On ordinal logistic regression, gestational diabetes mellitus, initial fraction of inspiration O2 value, invasive ventilation, acidosis, hypochloremia, C-reactive protein level, patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity. All the XGB, LR and RF models (AUC = 0.85, 0.86 and 0.84, respectively) all had good performance.ConclusionsWe found risk factors for BPD severity in our population and developed machine learning models based on them. The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.

Co-expression network analysis for identification of novel biomarkers of bronchopulmonary dysplasia model.

Bronchopulmonary dysplasia (BPD) is the most common neonatal chronic lung disease. However, its exact molecular pathogenesis is not understood. We aimed to identify relevant gene modules that may play crucial roles in the occurrence and development of BPD by weighted gene co-expression network analysis (WGCNA). We used RNA-Seq data of BPD and healthy control rats from our previous studies, wherein data from 30 samples was collected at days 1, 3, 7, 10, and 14. Data for preprocessing analysis included 17,613 differentially expressed genes (DEGs) with false discovery rate <0.05. We grouped the highly correlated genes into 13 modules, and constructed a network of mRNA gene associations, including the 150 most associated mRNA genes in each module. Lgals8, Srpra, Prtfdc1, and Thap11 were identified as the key hub genes. Enrichment analyses revealed Golgi vesicle transport, coated vesicle, actin-dependent ATPase activity and endoplasmic reticulum pathways associated with these genes involved in the pathological process of BPD in module. This is a study to analyze data obtained from BPD animal model at different time-points using WGCNA, to elucidate BPD-related susceptibility modules and disease-related genes.

Big Data for Tiny Patients: A Precision Medicine Approach to Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of extreme prematurity. Despite more than 50 years of research, current treatments are ineffective, and clinicians are largely unable to accurately predict which neonates the condition will develop in. A deeper understanding of the molecular mechanisms underlying the characteristic arrest in lung development are warranted. Integrating high-fidelity technology from precision medicine approaches may fill this gap and provide the tools necessary to identify biomarkers and targetable pathways. In this review, we describe insights garnered from current studies using omics for BPD prediction and stratification. We conclude by describing novel programs that will integrate multi-omics in efforts to better understand and treat the pathogenesis of BPD. [Pediatr Ann. 2022;51(10):e396-e404.].

Non-Tuberculous Mycobacteria and Aspergillus Lung Co-Infection: Systematic Review.

Non-tuberculous mycobacteria (NTM) and Aspergillus pulmonary co-infection occurs in patients with underlying lung disease and is rarely reported. We conducted a systematic search of NTM and Aspergillus pulmonary co-infection in PubMed, EMBASE, and Cochrane Library to identify cases published from 1977 to May 2022. We included 507 articles comprising 1538 cases (only 817 patients with partial relevant clinical data). Of these, 54.3% of patients were men, with a mean age of 57.7 years. Chronic obstructive pulmonary disease (21.1%), previous diagnosis of tuberculosis (18%), and asthma (11.1%) were the most common chronic lung diseases, and corticosteroids were used in 36.8% of patients. The most frequent symptoms were cough (68.2%), dyspnea (59.1%), and hemoptysis (34.1%). The most common radiological findings were bronchiectasis (52.3%) and cavitation (40.8%). NTM and Aspergillus were treated simultaneously in 47.3% of cases, whereas NTM-targeted therapy only was performed in 23.4% and Aspergillus only in 1.6%. The remaining 27.7% did not receive any treatment and were considered to be colonized. The global mortality rate was 43% (159/370). There was an increased prevalence of NTM and pulmonary aspergillosis among patients with underlying chronic lung diseases, which led to severe pulmonary affection with a poor global prognosis.

Non-standard therapeutic methods for severe bronchopulmonary dysplasia in a premature newborn – case report

Bronchopulmonary dysplasia is a lung disease that is the most common complication of prematurity and the most common chronic lung disease in neonates treated with mechanical ventilation and/or oxygen therapy. Children with bronchopulmonary dysplasia are at risk of cardiovascular complications, such as pulmonary arterial hypertension and left ventricular hypertrophy. The presented case concerns a premature infant born at 24 weeks gestation with severe bronchopulmonary dysplasia complicated by pulmonary arterial hypertension, interstitial emphysema and emphysema. The patient was subject to non-standard therapeutic procedures including L-citrulline, which may have a beneficial effect on the treatment of complications of severe bronchopulmonary dysplasia. Despite proper treatment, it is not always possible to avoid severe complications of bronchopulmonary dysplasia. Currently, available therapies are not always fully effective and it is necessary to continue searching and implementing new treatments to lower the risk of infant death and minimise long-term complications.

Pulmonary Delivery of Levamisole Nanoparticles as an Immunomodulator Affecting Th and a Potential ADAM10 Inhibitor to Ameliorate Severe Allergic Asthma.

Asthma is a common chronic lung disease without absolute treatment, and hypersensitivity reactions and type 2 immune responses are responsible for asthma pathophysiology. ADAM10 as a metalloproteinase transmembrane protein is critical for development of Th2 responses, and levamisole as an anthelmintic drug has immunomodulatory effects, which not only regulates ADAM10 activity but also can suppress the bone marrow and neutrophil production. Therefore, in the present study, nanoparticles were used as a levamisole delivery system to reduce bone marrow suppression, and the immunomodulatory and ADAM10 inhibitory effects of levamisole were studied in allergic asthma. Asthmatic mice were treated with PLGA-levamisole nanoparticles. Then, AHR, BALF, and blood cell counts, levels of the IgG1 subclass, total and OVA-specific IgE, IL2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-25, IL-33, INF-γ, and TNF-α, gene expression of FoxP3, T-bet, RORγt, PU.1, GATA3, FcεRII, CysLT1R, eotaxin, and ADAM10, and lung histopathology were evaluated. PLGA-LMHCl with considered characteristics could control airway hyper-responsiveness, eosinophils in the BALF, levels of immunoglobulins, Th2-, Th9-, and Th17-derived cytokines and pivotal genes, eosinophilic inflammation, hyperplasia of the goblet cell, and hyperproduction of mucus and could increase Th1- and Treg-derived cytokines and also pivotal genes. It could also modulate the ADAM10 activity and had no effect on the number of neutrophils in the bloodstream. The novel safe nanodrug had no side effect on the bone marrow to produce neutrophils and could control the allegro-immuno-inflammatory response of asthma.

Prevalence of bronchopulmonary dysplasia in the Russian Federation. Are the data real?

Bronchopulmonary dysplasia is the most common chronic lung disease in children under three years. Risk factors of bronchopulmonary dysplasia include prematurity, low birth weight, intrauterine growth restriction, and prolonged respiratory support in neonatal period. However, the incidence of bronchopulmonary dysplasia directly depends on the criteria for diagnosis and criteria for its withdrawal, since the most frequent current “new form” of the disease may not have clinically significant manifestations. This article summarizes data of bronchopulmonary dysplasia incidence in different medical centers in the Russian Federation. The incidence of bronchopulmonary dysplasia varied significantly from 0% to 87%. Increasing knowledge on incidence of bronchopulmonary dysplasia is important to determine ways to improve care of premature infants, to predict diseases of the respiratory system in these patients. It is possible to get reliable data in groups of patients homogeneous in terms of gestational age and birth weight if applying uniform approaches to the diagnosis and treatment of the disease.

Early Impairment of Right Ventricular Functions in Patients with Moderate Asthma and the Role of Isovolumic Acceleration

Introduction: Asthma is a common chronic lung disease that affects people all over the world. Pulmonary hypertension and right ventricular (RV) dysfunction are possible complications that may develop in the advanced stages of asthma. However, the number of studies investigating asthma and its implications on new RV parameters are very rare. This study aims to evaluate the RV functions in patients with moderate asthma before the development of pulmonary hypertension. Patients and Methods: Forty-one patients with moderate asthma and 40 healthy individuals were enrolled in this case-control study. All participants underwent a detailed two-dimensional echocardiographic examination. RV functions were measured through RV isovolumic acceleration (IVA) index in addition to conventional parameters. RV IVA, a tissue doppler derived parameter, was calculated as the ratio between maximum isovolumic myocardial velocity during isovolumic contraction and the time interval from the onset of this wave to the time at its maximum velocity. Results: There were no significant differences between the two groups in terms of baseline clinical characteristics, laboratory findings and echocardiographic parameters measuring left ventricular functions (p&gt; 0.05). In asthmatic patients, RV isovolumic relaxation time and RV myocardial performance index were higher (p= 0.027 and p&lt;0.001 respectively), while RV fractional area change, tricuspid annular plane systolic excursion (TAPSE) and RV IVA values were all lower (p&lt;0.001). RV IVA was found to be inversely proportional to asthma duration. TAPSE [β= 0.632, 95% CI= (0.121) - (0.225), p&lt;0.001] and pulmonary artery systolic pressure [β= -0.188, 95% CI= (-0.057) - (-0.003), p= 0.032] were shown as independent predictors of RV IVA. Conclusion: Asthma is an important disease that may result in subclinical RV dysfunction even before the development of pulmonary hypertension. RV IVA, an easily obtained and load-independent parameter, may be a useful and reliable index that sensitively analyzes subtle deteriorations in the contractile function of RV in asthmatic patients. RV IVA may also correlate with asthma duration.

LncRNA SNHG6 accelerates hyperoxia-induced lung cell injury via regulating miR-335 to activate KLF5/NF-κB pathway

BackgroundBronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, and its pathogenesis has not been clarified. Long non-coding RNAs (lncRNA) have important functions in cell bioactivity. However, their role in developmental lung disease remains unclear. ObjectiveThe aim of this study was to demonstrate the role of lncRNA SNHG6 (SNHG6) in BPD and its underlying mechanisms. MethodsThe blood of patients with BPD were collected, and BPD model of BEAS-2B cells was established by hyperoxia method. SNHG6, miR-335 and KLF5 mRNA expression were detected by RT-qPCR. Western blot was conducted to measure the levels of apoptosis-related proteins’ expression and NF-κB pathway related proteins. BEAS-2B cell viability and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Assay Kit was applied to detect ROS, MDA and SOD levels, respectively. ELISA was performed to assess the levels of inflammatory factors. The binding site of miR-335 with SNHG6 or KLF5 were predicted by using DIANA or TargetScan, and which was verified by double luciferase reporter assay. ResultsFirstly, SNHG6 was highly expressed and miR-335 was lowly expressed in BPD model, SNHG6 knockdown and miR-335 mimics both alleviated hyperoxia-induced lung cell injury, and SNHG6 targeted miR-335. Subsequently, KLF5 was targeted by miR-335, and KLF5 promoted lung cell injury via activating NF-κB pathway. Furthermore, SNHG6 mediated lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. ConclusionOur research confirmed that SNHG6 mediated hyperoxia-induced lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. These findings suggest that SNHG6 serves as promising targets for the treatment of newborns with BPD.

Chronic bronchitis in the practice of a family doctor

Chronic bronchitis is the most common chronic nonspecific lung disease (CNSLD). The prevalence of chronic bronchitis in the Russian Federation ranges from 10 to 20%, and the increase in the incidence of chronic nonspecific lung diseases is 6–7% for the urban and 2–3% for the rural population per year. The recent increase in the incidence of bronchitis in most countries of the world is associated with air pollution with dust particles and gases, the popularity of smoking, and allergies of the population. The article tells about the modern principles of diagnosis and treatment of chronic bronchitis. Particular attention is paid not only to the optimal choice of antibiotic therapy for infectious exacerbation of chronic bronchitis (CB), but also to the role of topical antibacterial drugs (ABD) in this case. The basic points outlined in the article can be useful for general practitioners and pulmonologists who are faced with this disease.

DOCK2 contributes to pulmonary fibrosis by promoting lung fibroblast to myofibroblast transition.

Idiopathic pulmonary fibrosis (IPF) is the most common chronic interstitial lung disease and is characterized by progressive scarring of the lung. Transforming growth factor-β (TGF-β) signaling plays an essential role in IPF and drives fibroblast to myofibroblast transition (FMT). Dedicator of cytokinesis 2 (DOCK2) is known to regulate diverse immune functions by activating Rac and has been recently implicated in pleural fibrosis. We now report a novel role of DOCK2 in pulmonary fibrosis development by mediating FMT. In primary normal and IPF human lung fibroblasts (HLFs), TGF-β induced DOCK2 expression concurrent with FMT markers, smooth muscle α-actin (α-SMA), collagen-1, and fibronectin. Knockdown of DOCK2 significantly attenuated TGF-β-induced expression of these FMT markers. In addition, we found that the upregulation of DOCK2 by TGF-β is dependent on both Smad3 and ERK pathways as their respective inhibitors blocked TGF-β-mediated induction. TGF-β also stabilized DOCK2 protein, which contributes to increased DOCK2 expression. In addition, DOCK2 was also dramatically induced in the lungs of patients with IPF and in bleomycin, and TGF-β induced pulmonary fibrosis in C57BL/6 mice. Furthermore, increased lung DOCK2 expression colocalized with the FMT marker α-SMA in the bleomycin-induced pulmonary fibrosis model, implicating DOCK2 in the regulation of lung fibroblast phenotypic changes. Importantly, DOCK2 deficiency also attenuated bleomycin-induced pulmonary fibrosis and α-SMA expression. Taken together, our study demonstrates a novel role of DOCK2 in pulmonary fibrosis by modulating FMT and suggests that targeting DOCK2 may present a potential therapeutic strategy for the prevention or treatment of IPF.