scholarly journals Effect of TRPM8 and TRPA1 Polymorphisms on COPD Predisposition and Lung Function in COPD Patients

2021 ◽  
Vol 11 (2) ◽  
pp. 108
Author(s):  
Denis E. Naumov ◽  
Olesya O. Kotova ◽  
Dina A. Gassan ◽  
Ivana Y. Sugaylo ◽  
Evgeniya Y. Afanas’eva ◽  
...  

Certain transient receptor potential (TRP) channels including TRPM8 and TRPA1 are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter—the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%. Lung function was measured by spirometry. TRPM8 and TRPA1 polymorphisms were genotyped by LATE-PCR. None of the polymorphisms significantly influenced COPD predisposition after correction for covariates and multiple testing. Among COPD patients, the TT genotype of TRPA1 rs7819749 was significantly associated with higher degree of bronchial obstruction. In addition, we established that carriers of the C allele of TRPM8 rs11562975 more commonly had post-bronchodilator FEV1 < 60% (OR 3.2, 95%CI (1.14–8.94), p = 0.03) and revealed the effect of TRPA1 rs959976 and TRPM8 rs17865682 on bronchodilator response in COPD. Thus, the obtained results suggest possible involvement of TRPM8 and TRPA1 in COPD pathogenesis, indicating the necessity to further investigate their functional role in this pathology.

2019 ◽  
Vol 8 (4) ◽  
pp. 562
Author(s):  
Hung-Yu Huang ◽  
Chun-Yu Lo ◽  
Lan-Yan Yang ◽  
Fu-Tsai Chung ◽  
Te-Fang Sheng ◽  
...  

Negative pressure ventilation (NPV), when used as an adjuvant to pulmonary rehabilitation, improves lung function, increases exercise capacity, and reduces exacerbations. The aim of this study was to determine whether maintenance NPV improves long-term clinical outcomes and reduces mortality in patients with chronic obstructive pulmonary disease (COPD). Between 2003 and 2009, 341 patients were treated for COPD either with or without hospital-based NPV. We measured forced expiratory volume in one second (FEV1), 6-min walking distance (6MWD), and oxygen saturation by pulse oximetry (SpO2) during a 6-min walk test (6MWT) every 3–6 months. Desaturation (D) during the 6MWT was defined as a reduction in SpO2 of ≥10% from baseline. The NPV group had a better survival outcome than the Non-NPV group. The 8-year survival probabilities for the NPV and Non-NPV groups were 60% and 20%, respectively (p < 0.01). Baseline desaturation was a significant risk factor for death, and the risk of death increased with desaturation severity (SpO2 80~89: hazard ratios (HR) 2.7, 95% confidence interval (CI) 1.4–5.3; SpO2 < 80: HR 3.1, 95% CI 1.3–7.4). The NPV group had a slower decline in lung function and 6MWD. The NPV + D and Non-NPV+D had a threefold and fourfold increase in the risks of all-cause mortality compared with the NPV-ND, respectively. Maintenance non-invasive NPV reduced long-term mortality in COPD patients. The desaturating COPD patients had an increased mortality risk compared with non-desaturating COPD patients.


2019 ◽  
Vol 12 (1) ◽  
pp. 23 ◽  
Author(s):  
Alexander Dietrich

The lungs are essential for gas exchange and serve as the gateways of our body to the external environment. They are easily accessible for drugs from both sides, the airways and the vasculature. Recent literature provides evidence for a role of Transient Receptor Potential (TRP) channels as chemosensors and essential members of signal transduction cascades in stress-induced cellular responses. This review will focus on TRP channels (TRPA1, TRPC6, TRPV1, and TRPV4), predominantly expressed in non-neuronal lung tissues and their involvement in pathways associated with diseases like asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), lung fibrosis, and edema formation. Recently identified specific modulators of these channels and their potential as new therapeutic options as well as strategies for a causal treatment based on the mechanistic understanding of molecular events will also be evaluated.


2017 ◽  
Vol 49 (5) ◽  
pp. 1602008 ◽  
Author(s):  
Tobias N. Bonten ◽  
Marise J. Kasteleyn ◽  
Renee de Mutsert ◽  
Pieter S. Hiemstra ◽  
Frits R. Rosendaal ◽  
...  

Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) seems an important clinical phenotype, but multiple definitions have been proposed. This study's objectives were to assess the effect of different ACOS definitions on prevalence, patient characteristics and exacerbations.5675 individuals aged 45–65 years, with 846 asthma/COPD patients, were included in the Netherlands Epidemiology of Obesity study between 2008 and 2012, and followed-up for a median of 1.8 years. ACOS was defined by recent consensus criteria and five other definitions, based on registry, questionnaires and lung function.Prevalence of ACOS in the asthma/COPD population ranged between 4.4% and 38.3%, depending on the definition used. Agreement between registry-based and self-reported ACOS was 0.04 and 0.41 when lung function (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) was added. With registry or self-report defined ACOS, only 51% and 33% had FEV1/FVC <0.7. Patient characteristics were similar, but asthma duration was longer with self-reported compared with registry-based ACOS (mean difference 22 years (95% CI 12–33)). Exacerbation risk was highest with registry-based ACOS compared with asthma (adjusted incidence rate ratio 1.6 (95% CI 1.2–2.1)).This study adds important knowledge about agreement between ACOS definitions and their relation with exacerbations. Given the low agreement, differences in prevalence, patient characteristics and risk of exacerbations, consensus about ACOS definition in different care settings is urgently needed.


2015 ◽  
Vol 10 ◽  
Author(s):  
Giorgio Fumagalli ◽  
Fabrizio Fabiani ◽  
Silvia Forte ◽  
Massimiliano Napolitano ◽  
Giovanni Balzano ◽  
...  

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by respiratory and extrarespiratory components referring both to systemic complications of COPD, like skeletal muscle myopathy, weight loss and others, and frequently associated comorbidities, interesting various organs and systems (cardiovascular diseases, malignancies, osteoporosis, diabetes, etc.). These comorbidities may increase the rate of hospitalization of COPD patients and have a huge effect on the outcomes of the respiratory disease. Inhalation therapy of COPD with bronchodilators and steroid is primary driven by airflow obstruction, symptoms like dyspnoea, and acute exacerbations. INDACO project has been developed in 2013 to assess the prevalence and type of comorbidities in COPD patients referred to the outpatient wards of some hospitals in Central and South Italy and a preliminary report has recently been published. In the present study, after widening that database, we evaluate the prevalence of comorbidities and the relationships between comorbidities and sex, age, symptoms, lung function and inhalation therapy in COPD patients. Methods: In each enrolled patient, anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for Chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI) were recorded. Results: We collected data of 569 patients (395 males and 174 females, mean age 73 ± 8.5 yrs). The prevalence of patients with comorbidities was 81.2%. Overall number of comorbidities was not related to airflow obstruction and age, but to acute exacerbation of COPD, dyspnoea measured with MRC scale, and male gender. A subgroup analysis revealed that ischaemic heart disease was predominant in males, whereas mood disorders in females. The use of a more complex (multi-drug) inhalation therapy was related with bronchial obstruction measured by FEV1/FVC (p for trend = 0.003) and number of comorbidities (p for trend = 0.001). In multivariate analysis, only airflow obstruction and number of comorbidities were determinant of complexity of therapy, but not MRC and acute exacerbation of COPD. However, the statistical model reached an extreme low degree of significance (r^2 = 0.07). Conclusions: Our study showed a high prevalence of comorbidities in COPD, with some differences related to gender. Number of comorbidities and airflow obstruction represent the determinant of inhalation therapy prescription. Dyspnoea and acute exacerbation of COPD, unlikely suggested by guidelines, are not significant drivers of therapy in the real life setting of our study.


2015 ◽  
Vol 79 (3-4) ◽  
Author(s):  
Biagio Polla

We present a case of a 85-year-old man who suffered from several chronic obstructive pulmonary disease (COPD) related exacerbations and hospitalizations. Traditional therapy, which also included intramuscular steroid therapy, did not help and caused several drug related adverse events. After yet another exacerbation followed by hospitalization at the intensive care unit, it was decided to start roflumilast treatment. In the year after beginning treatment, the patient did not experience any more exacerbations and his lung function also improved, as recorded by the COPD assessment test (CAT) score and improved forced expiratory volume in the first second (FEV1) value. In this patient roflumilast seems to be effective in reducing exacerbations, an important goal to be achieved in COPD patients.


2015 ◽  
Vol 79 (3-4) ◽  
Author(s):  
Andrea Zanini ◽  
Francesca Cherubino ◽  
Patrizia Pignatti

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Chronic inflammation and exacerbations play a central role in the progression of the disease. Currently, treatment options for COPD have been shown to improve the progressive decline in lung-function and/or decrease mortality rates. Roflumilast, a phosphodiesterase- 4 inhibitor, is an anti-inflammatory drug which has been licensed as an add-on therapy for COPD patients with forced expiratory volume in the first second &lt;50% and frequent exacerbations. Clinical trials have demonstrated that roflumilast improves lung function and reduces exacerbation frequency. Roflumilast has a mechanism of action which allows it to obtain a significant additive effect to current therapeutic options for COPD patients. It is generally well tolerated, although the most common adverse effects include diarrhea, nausea, weight loss, and headache. This review article provides an overview of the positive effects of roflumilast on lung function, exacerbation frequency and glucose metabolism, and its interaction with concomitant inhaled treatments.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sun Hye Shin ◽  
Sumin Shin ◽  
Yunjoo Im ◽  
Genehee Lee ◽  
Byeong-Ho Jeong ◽  
...  

AbstractChronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.


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