Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

Rodrigues, Sarah de Oliveira; Cunha, Carolina Medina Coeli da; Soares, Giovanna Martins Valladão; Silva, Pedro L.; Silva, Adriana Ribeiro; Gonçalves-de-Albuquerque, Cassiano Felippe

doi:10.3390/ph14100979

Cited by 51 publications

(22 citation statements)

References 262 publications

(328 reference statements)

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“…Dexamethasone-induced inhibition of chemotactic factors may result in a reduction of neutrophil margination and influx into the lungs, with their simultaneous increase in the blood (36,37) as also demonstrated in our previous studies (34,35). On the other hand, the potential of dexamethasone to reduce the numbers of eosinophils, neutrophils and lymphocytes in the blood and BAL fluid shown in our study is in agreement with the action of corticosteroids in the treatment of other respiratory diseases including bronchial asthma (38)(39)(40), chronic obstructive pulmonary disease (41)(42)(43), community-aquired pneumonia (44), or various types of acute lung injury (45).…”

Section: Discussionsupporting

confidence: 90%

Effects of early dexamethasone treatment on several markers of inflammation and fibrosis in an animal model of lung silicosis in rats – A pilot study

Adamcakova

Bálentová

Hanusrichterova

et al. 2022

Acta Medica Martiniana

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Lung silicosis is primarily caused by inhalation of particles of silicon oxide (silica). Despite a huge progress in understanding the interactions among the pathomechanisms of lung silicosis in the last years, there is a lack of effective therapy. With respect to a wide therapeutic action of corticosteroids, the purpose of this pilot study was to evaluate early effects of dexamethasone on several markers of inflammation and lung fibrosis in a rat model of silicosis. The silicosis model was induced by a single transoral intratracheal instillation of silica (50 mg/ml/animal), while the controls received an equivalent volume of sterile saline. The treatment with intraperitoneal dexamethasone initiated the next day after the silica instillation and was given 2-times a week at a dose of 1 mg/kg, while the controls received an equivalent volume of saline. The animals were euthanized 14 or 28 days after the treatment onset. Total and differential counts of leukocytes in the blood and bronchoalveolar lavage (BAL) fluid were determined. The presence of collagen in the bronchioles and lung vessels was detected by Sirius red staining and a smooth muscle mass was detected by smooth muscle actin. In comparison to saline, the instillation of silica increased the total count of circulating leukocytes after 14 and 28 days of the experiment (both p<0.05), which was associated with higher counts of lymphocytes (p<0.05 after 14 days, p>0.05 after 28 days) and slight but non-significant increases in neutrophils and eosinophils (both p>0.05). Although the total cell count in the BAL fluid did not change significantly, the percentages and absolute counts of neutrophils, eosinophils, and lymphocytes (p<0.05, p<0.01 or p<0.001) elevated after 14 and 28 days of the experiment. Silica induced an accumulation of collagen in the bronchioles (p<0.001 after both 14 and 28 days) and pulmonary vessels (p<0.01 after both 14 and 28 days) and elevated a formation of smooth muscle mass (p<0.05 after 14 days, p<0.01 or p<0.001 after 28 days). Treatment with dexamethasone decreased circulating leukocytes (p<0.01) and lymphocytes (p<0.001) and increased neutrophils (p<0.05), which was associated with a slightly decreased total cell count in BAL (p>0.05), decline in lymphocytes (p<0.01), and slight decreases in neutrophils and eosinophils after 28 days of the treatment. Moreover, dexamethasone reduced the accumulation of collagen (p<0.01 after 14 days and p<0.001 after 28 days) and the formation of smooth muscle mass (p<0.01 for bronchioles and p>0.05 for vessels after 24 days, p<0.001 for both bronchioles and vessels after 28 days). In conclusion, early dexamethasone treatment mitigated silica-induced granulocytic-lymphocytic inflammation and decreased a formation of collagen and smooth muscle mass in the bronchiolar and vascular walls, demonstrating a therapeutic potential of dexamethasone in the lung silicosis.

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Section: Discussionsupporting

confidence: 90%

Effects of early dexamethasone treatment on several markers of inflammation and fibrosis in an animal model of lung silicosis in rats – A pilot study

Adamcakova

Bálentová

Hanusrichterova

et al. 2022

Acta Medica Martiniana

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“…However, these therapies do not effectively halt disease progression [1]. Due to the complexity of its pathophysiology, non-pharmacologic interventions (e.g., physical activity) can have significant effects in improving the quality of life and prognosis, with favorable socioeconomic benefits [5].…”

Section: Introductionmentioning

confidence: 99%

Physical activity and chronic obstructive pulmonary disease: a scoping review

Xiang

Fang

et al. 2022

BMC Pulm Med

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Background Reduced physical activity (PA) was the strongest predictor of all-cause mortality in patients with chronic obstructive pulmonary disease (COPD). This scoping review aimed to map the evidence on the current landscape of physical activity, barriers and facilitators, and assessment tools across COPD patients. Methods Arksey and O’Malley’s scoping review methodology framework guided the conduct of this review. An electronic search was conducted on five English databases (PubMed, Cochrane Library, PsycINFO, CINAHL and Web of Science) and three Chinese databases (CNKI, CQVIP and WAN-FANG) in January 2022. Two authors independently screened the literature, extracted the studies characteristics. Results The initial search yielded 4389 results, of which 1954 were duplicates. Of the remaining 135 articles, 42 studies met the inclusion criteria. Among the reviewed articles, there were 14 (33.3%) cross-sectional study, 9 (21.4%) cohort study, 4 (9.5%) longitudinal study, 3 qualitative study, 12 (28.7%) randomized control trials. The main barriers identified were older age, women, lung function, comorbidities, COPD symptoms (fear of breathlessness and injury, severe fatigue, anxiety and depression), GOLD stage, frequency of exacerbation, oxygen use, lack of motivation and environment-related (e.g., season and weather). Twelve studies have evaluated the effects of physical exercise (e.g., walking training, pulmonary rehabilitation (PR), pedometer, self-efficacy enhancing intervention and behavioral modification intervention) on PA and showed significant positive effects on the prognosis of patients. However, in real life it is difficult to maintain PA in people with COPD. Conclusions Changing PA behavior in patients with COPD requires multidisciplinary collaboration. Future studies need to identify the best instruments to measure physical activity in clinical practice. Future studies should focus on the effects of different types, time and intensity of PA in people with COPD and conduct randomized, adequately-powered, controlled trials to evaluate the long-term effectiveness of behavioral change interventions in PA.

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“…First, bronchodilators can increase oxygenation function by improving the essential symptoms or respiratory status of COPD. [24,25] Second, bronchodilators have a stimulating effect (or even an promoting effect) on the central nervous system. For example, short-acting beta-2 agonists have been reported to reduce stress and feelings of fear after tra c accidents [2].…”

Section: Discussionmentioning

confidence: 99%

The adjusted impact of different severities of acute exacerbations and medications on the risk of suffering dementia in COPD patients

Chia

Chang

Chen

et al. 2022

Preprint

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Background: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used (for COPD) are not well evaluated as risk factors for increasing (or decreasing) dementia occurrence. We aimed to analyze the impact of different severities of COPD acute exacerbations (AEs) and different medications on the risk of suffering dementia in COPD patients.Method: This study was a 5-year follow-up of the Taiwanese government deidentified health-care database (from January 1, 2000, to December 31, 2010). The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Demographics, baseline comorbidities, medications (antibiotics, bronchodilators, corticosteroids), and the severity upon initial ED visit (only ED treatment, hospital admission, or ICU admission) were all considered confounding factors between the two groups.Results: Among the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatments obviously decreased the HRs, especially in those who received long-term (>1 month) treatment (HR=2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 COPD AE patients who initially visited the and ED, patients who required ICU admission (n=164, 4.7%) were at a very high risk of dementia occurrence (HR=11.05, 95% CI: 7.77-15.71).Conclusion: Long-term bronchodilator administration was associated with a decreased risk of suffering dementia. More importantly, patients who suffered COPD AEs and initially visited the ED and required ICU admission were at a very high risk of developing dementia.

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Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

Cited by 51 publications

References 262 publications

Effects of early dexamethasone treatment on several markers of inflammation and fibrosis in an animal model of lung silicosis in rats – A pilot study

Effects of early dexamethasone treatment on several markers of inflammation and fibrosis in an animal model of lung silicosis in rats – A pilot study

Physical activity and chronic obstructive pulmonary disease: a scoping review

The adjusted impact of different severities of acute exacerbations and medications on the risk of suffering dementia in COPD patients

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