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1.
PLoS One ; 18(6): e0286870, 2023.
Article in English | MEDLINE | ID: covidwho-20239895

ABSTRACT

BACKGROUND: Incorrect use of inhalers is a problem associated with poor patient outcomes. Despite improvement in the technique after verbal educations, this deteriorates over-time requiring re-enforcement through different educative strategies. This study aimed to assess the impact of a novel video-based teach-to-goal (TTG) educational intervention on: mastery of inhaler technique, disease control, medication adherence and disease-related quality of life (QoL) over-time among asthma and COPD patients. METHODS: This prospective, open-label, randomized controlled trial was registered in ClinicalTrials.gov: Identifier NCT05664347. After baseline assessment participants received either a verbal (control group) or a video-based (intervention group) TTG strategy. After 3-month the intervention was assessed for impact on the intended outcomes. Inhaler technique was assessed using standardized checklists, disease control using the Asthma control test and COPD assessment test respectively for asthma and COPD patients while adherence using the Morisky Green Levine scale. For QoL, the mini asthma quality of life questionnaire and the St. George respiratory questionnaire were used for asthmatic and COPD patients, respectively. Differences in outcomes between intervention-control groups were analyzed using either Chi-Square (X2)/Fisher Exact or Mann Whitney test. The impact of intervention on outcomes over-time was examined using either McNemar or Wilcoxon test. RESULTS: At baseline, intervention (n = 51) and control (n = 52) groups had comparable demographic/clinical characteristics. At follow-up, inhaler technique improved among intervention group compared to control group (93.4% vs 67%) and to baseline (93.4% to 49.5%), (P<0.05). Similarly, medication adherence ameliorated among the intervention group in comparison to control group (88.2% to 61.5%) and to baseline (88.2% to 66.7%), (P<0.05). In regards to disease control, results showed an amelioration among the intervention group compared to baseline (35.3% to 54.9%) (P<0.05). QoL scores improved significantly among asthma patients (intervention group) at follow-up vs baseline. Better scores were also observed for COPD patients compared to controls, (P<0.05). CONCLUSION: Video-based (TTG) was effective in enhancing inhaler technique over time as well as improving disease control, medication adherence, and QoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05664347. https://clinicaltrials.gov/ct2/show/NCT05664347.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Adult , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , Prospective Studies , Goals , Administration, Inhalation , Asthma/drug therapy , Nebulizers and Vaporizers
2.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2606-2612, 2023 May.
Article in Chinese | MEDLINE | ID: covidwho-20244902

ABSTRACT

Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic herbal formula. All of them are derived from Treatise on Cold Damage(Shang Han Lun) by ZHANG Zhong-jing. This combination has the effects of harmonizing lesser yang, relieving exterior syndrome, clearing lung heat, and relieving panting. It is mainly used for treating the disease involving the triple-Yang combination of diseases and accumulation of pathogenic heat in the lung. Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic combination for the treatment of exogenous diseases involving the triple-Yang combination. They are commonly used in exogenous diseases, especially in the north of China. This combination is also the main treatment strategy for coronavirus disease 2019(COVID-19) accompanied by fever and cough. Maxing Shigan Decoction is a classical herbal formula for treating the syndrome of phlegm-heat obstructing the lung. "Dyspnea after sweating" suggests the accumulation of pathogenic heat in the lung. Patients with mild symptoms may develop cough and asthma along with forehead sweating, and those in critical severe may develop whole-body sweating, especially the front chest. Modern medicine believes that the above situation is related to lung infection. "Mild fever" refers to syndromes rather than pathogenesis. It does not mean that the heat syndrome is not heavy, instead, it suggests that severe heat and inflammation have occurred. The indications of Xiao Chaihu Decoction combined with Maxing Shigan Decoction are as follows.(1) In terms of diseases, it is suitable for the treatment of viral pneumonia, bronchopneumonia, lobar pneumonia, mycoplasma pneumonia, COVID-19 infection, measles with pneumonia, severe acute respiratory syndrome(SARS), avian influenza, H1N1 influenza, chronic obstructive pulmonary disease with acute exacerbation, pertussis, and other influenza and pneumonia.(2) In terms of syndromes, it can be used for the syndromes of bitter mouth, dry pharynx, vertigo, loss of appetite, vexation, vomiting, and fullness and discomfort in the chest and hypochondrium. It can also be used to treat alternate attacks of chill and fever and different degrees of fever, as well as chest tightness, cough, asthma, expectoration, dry mouth, wanting cold drinks, feeling agitated, sweating, yellow urine, dry stool, red tongue, yellow or white fur, and floating, smooth, and powerful pulse, especially the right wrist pulse.


Subject(s)
Asthma , COVID-19 , Drugs, Chinese Herbal , Influenza A Virus, H1N1 Subtype , Influenza, Human , Pulmonary Disease, Chronic Obstructive , Animals , Humans , Cough , Syndrome , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Lung , Pulmonary Disease, Chronic Obstructive/drug therapy , Critical Care , Medicine, Chinese Traditional
3.
Orv Hetil ; 164(2): 43-50, 2023 Jan 15.
Article in Hungarian | MEDLINE | ID: covidwho-2300132

ABSTRACT

INTRODUCTION: Literature data show an increased severity of SARS-CoV-2 infection in patients with cardiovascular, renal comorbidities, chronic obstructive pulmonary disease (COPD), asthma, obesity, diabetes, tumors and immunosuppression. METHOD: This retrospective study includes 90 patients with SARS-CoV-2 infection associated with COPD or asthma exacerbations from 303 patients hospitalized during a 7-month period (29.7%). The clinical aspect of COPD/asthma exacerbations overlapped to the one by SARS-CoV-2 infection, therefore, we compared our group with 90 patients with SARS-CoV-2 without obstructive disease. We excluded from both groups the patients with known severe cardiac impairment, diabetes, or tumors in order to not having interference with other unfavorable prognostic factors. We assessed the cases severity on clinical basis, pulzoximetry, CT/chest x-ray, and inflammatory markers. RESULTS: 72.2% of our group (48/52 with COPD and 17/38 with asthma) had moderate/severe pneumonia (bilateral interstitial-alveolar infiltrates, increased inflammatory markers, respiratory dysfunction) compared with 56.6% from the nonobstructive group. 14 patients required intensive therapy (including mechanical ventilation). We recorded 4 deaths in COPD group, 1 in asthma group, compared to 2 in non-obstructive patients (fatality 7.6% in COPD compared to 2.2% in nonobstructive group). Treatment included maximized inhaled bronchodilators ± corticosteroids, oxygen, antivirals, anticoagulants, corticosteroids, symptomatic. All patients were referred for clinical-functional and CT scan reassessment 2 months after discharge. CONCLUSION: The association of SARS-CoV-2 infection in patients with COPD or asthma was common, leading to exacerbation with significant severity. Fatality increased in COPD. Outpatient follow-up aims to restage adjust the treatment and monitor post-COVID-19 possible sequels. Orv Hetil. 2023; 164(2): 43-50.


Subject(s)
Asthma , COVID-19 , Diabetes Mellitus , Pulmonary Disease, Chronic Obstructive , Pulmonary Medicine , Humans , COVID-19/complications , COVID-19/therapy , SARS-CoV-2 , Retrospective Studies , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/complications , Adrenal Cortex Hormones/therapeutic use
4.
Respir Investig ; 61(2): 270-283, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2287419

ABSTRACT

Respiratory viruses like rhinovirus, influenza virus, respiratory syncytial virus, and coronavirus cause several respiratory diseases, such as bronchitis, pneumonia, pulmonary fibrosis, and coronavirus disease 2019, and exacerbate bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, and diffuse panbronchiolitis. The production of inflammatory mediators and mucin and the accumulation of inflammatory cells have been reported in patients with viral infection-induced respiratory diseases. Interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and regulated on activation normal T-cell expressed and secreted are produced in the cells, including human airway and alveolar epithelial cells, partly through the activation of toll-like receptors, nuclear factor kappa B and p44/42 mitogen-activated protein kinase. These mediators are associated with the development of viral infection-induced respiratory diseases through the induction of inflammation and injury in the airway and lung, airway remodeling and hyperresponsiveness, and mucus secretion. Medications used to treat respiratory diseases, including corticosteroids, long-acting ß2-agonists, long-acting muscarinic antagonists, mucolytic agents, antiviral drugs for severe acute respiratory syndrome coronavirus 2 and influenza virus, macrolides, and Kampo medicines, reduce the production of viral infection-induced mediators, including cytokines and mucin, as determined in clinical, in vivo, or in vitro studies. These results suggest that the anti-inflammatory effects of these medications on viral infection-induced respiratory diseases may be associated with clinical benefits, such as improvements in symptoms, quality of life, and mortality rate, and can prevent hospitalization and the exacerbation of chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, and diffuse panbronchiolitis.


Subject(s)
Asthma , Bronchiectasis , COVID-19 , Pulmonary Disease, Chronic Obstructive , Virus Diseases , Humans , Quality of Life , Asthma/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Virus Diseases/drug therapy , Anti-Inflammatory Agents/therapeutic use , Mucins/therapeutic use
5.
Biomed Pharmacother ; 158: 114096, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2257259

ABSTRACT

BACKGROUND: Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. METHODS: The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. RESULTS: Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-ß/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. CONCLUSION: This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases.


Subject(s)
Asthma , Ginsenosides , Hypertension, Pulmonary , Influenza, Human , Lung Neoplasms , Panax , Pulmonary Disease, Chronic Obstructive , Pulmonary Fibrosis , Humans , Ginsenosides/pharmacology , Ginsenosides/therapeutic use , Ginsenosides/chemistry , Pulmonary Fibrosis/drug therapy , Hypertension, Pulmonary/drug therapy , Influenza, Human/drug therapy , Phosphatidylinositol 3-Kinases , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/drug therapy , Lung Neoplasms/drug therapy , Panax/chemistry
6.
Thorax ; 78(6): 543-550, 2023 06.
Article in English | MEDLINE | ID: covidwho-2252884

ABSTRACT

INTRODUCTION: Incorporating spirometry into low-dose CT (LDCT) screening for lung cancer may help identify people with undiagnosed chronic obstructive pulmonary disease (COPD), although the downstream impacts are not well described. METHODS: Participants attending a Lung Health Check (LHC) as part of the Yorkshire Lung Screening Trial were offered spirometry alongside LDCT screening. Results were communicated to the general practitioner (GP), and those with unexplained symptomatic airflow obstruction (AO) fulfilling agreed criteria were referred to the Leeds Community Respiratory Team (CRT) for assessment and treatment. Primary care records were reviewed to determine changes to diagnostic coding and pharmacotherapy. RESULTS: Of 2391 LHC participants undergoing prebronchodilator spirometry, 201 (8.4%) fulfilled the CRT referral criteria of which 151 were invited for further assessment. Ninety seven participants were subsequently reviewed by the CRT, 46 declined assessment and 8 had already been seen by their GP at the time of CRT contact. Overall 70 participants had postbronchodilator spirometry checked, of whom 20 (29%) did not have AO. Considering the whole cohort referred to the CRT (but excluding those without AO postbronchodilation), 59 had a new GP COPD code, 56 commenced new pharmacotherapy and 5 were underwent pulmonary rehabilitation (comprising 2.5%, 2.3% and 0.2% of the 2391 participants undergoing LHC spirometry). CONCLUSIONS: Delivering spirometry alongside lung cancer screening may facilitate earlier diagnosis of COPD. However, this study highlights the importance of confirming AO by postbronchodilator spirometry prior to diagnosing and treating patients with COPD and illustrates some downstream challenges in acting on spirometry collected during an LHC.


Subject(s)
Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Early Detection of Cancer , Smoking , Lung , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Treatment Outcome , Spirometry , Mass Screening/methods , Forced Expiratory Volume
7.
Int J Chron Obstruct Pulmon Dis ; 17: 2329-2341, 2022.
Article in English | MEDLINE | ID: covidwho-2237160

ABSTRACT

Purpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups. Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters. Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P<0.001), the COPD Assessment Test (CAT) score (20 vs 17, P<0.001), the blood eosinophil percentage (1.5 vs 2.0, P<0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥9 years), more symptoms (CAT ≥10), and lower blood eosinophils (Eos <2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations. Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Disease Progression , Humans , Patient Readmission , Propensity Score , Prospective Studies , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/therapy
8.
Eur J Med Chem ; 250: 115175, 2023 Mar 15.
Article in English | MEDLINE | ID: covidwho-2237130

ABSTRACT

C-X-C motif chemokine receptor 2 (CXCR2) is G protein-coupled receptor (GPCR) and plays important roles in various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), atherosclerosis, asthma, and pancreatic cancer. Upregulation of CXCR2 is closely associated with the migration of neutrophils and monocytes. To date, many small-molecule CXCR2 antagonists have entered clinical trials, showing favorable safety and therapeutic effects. Hence, we provide an overview containing the discovery history, protein structure, signaling pathways, biological functions, structure-activity relationships and clinical significance of CXCR2 antagonists in inflammatory diseases and cancers. According to the latest development and recent clinical progress of CXCR2 small molecule antagonists, we speculated that CXCR2 can be used as a biomarker and a new target for diabetes and that CXCR2 antagonists may also attenuate lung injury in coronavirus disease 2019 (COVID-19).


Subject(s)
Asthma , COVID-19 , Pancreatic Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Neutrophils/metabolism , Asthma/metabolism , Receptors, Interleukin-8B , Pancreatic Neoplasms/metabolism
9.
Mayo Clin Proc ; 98(2): 301-315, 2023 02.
Article in English | MEDLINE | ID: covidwho-2221124

ABSTRACT

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-ß2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with LAMA/LABA dual therapy. In IMPACT, fluticasone furoate/umeclidinium/vilanterol therapy significantly reduced the risk of on-/off-treatment all-cause mortality vs umeclidinium/vilanterol (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=.042). The ETHOS trial found a reduction in the risk of on-/off-treatment all-cause mortality in patients treated with budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol (hazard ratio, 0.51 [0.33 to 0.80]; nominal P=.0035). Both trials included populations of patients with symptomatic COPD at high risk of future exacerbations, and a post hoc analysis of the final retrieved vital status data suggested that the observed mortality benefits are conferred by the ICS component. In conclusion, triple therapy reduces the risk of mortality in patients with symptomatic COPD characterized by moderate or severe airflow obstruction and a recent history of moderate or severe exacerbations. This benefit is likely to be driven by reductions in exacerbations. Future research efforts should focus on improving the long-term prognosis of patients living with COPD.


Subject(s)
Drug Therapy, Combination , Pulmonary Disease, Chronic Obstructive , Humans , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Bronchodilator Agents , COVID-19 , Formoterol Fumarate/therapeutic use , Glycopyrrolate/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Drug Therapy, Combination/adverse effects
12.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2139130

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused severe illness and mortality for millions worldwide. Despite the development, approval and rollout of vaccination programmes globally to prevent infection by SARS-CoV-2 and the development of coronavirus disease 2019 (COVID-19), treatments are still urgently needed to improve outcomes. Early in the pandemic it was observed that patients with pre-existing asthma or COPD were underrepresented among those with COVID-19. Evidence from clinical studies indicates that the inhaled corticosteroids (ICS) routinely taken for asthma and COPD could have had a protective role in preventing severe COVID-19 and, therefore, may be a promising treatment for COVID-19. This review summarises the evidence supporting the beneficial effects of ICS on outcomes in patients with COVID-19 and explores the potential protective mechanisms.


Subject(s)
Asthma , COVID-19 , Pulmonary Disease, Chronic Obstructive , Humans , SARS-CoV-2 , Adrenal Cortex Hormones/adverse effects , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology
13.
Cell Commun Signal ; 20(1): 173, 2022 11 01.
Article in English | MEDLINE | ID: covidwho-2098351

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been growing swiftly worldwide. Patients with background chronic pulmonary inflammations such as asthma or chronic obstructive pulmonary diseases (COPD) are likely to be infected with this virus. Of note, there is an argument that COVID-19 can remain with serious complications like fibrosis or other pathological changes in the pulmonary tissue of patients with chronic diseases. Along with conventional medications, regenerative medicine, and cell-based therapy could be alternative approaches to compensate for organ loss or restore injured sites using different stem cell types. Owing to unique differentiation capacity and paracrine activity, these cells can accelerate the healing procedure. In this review article, we have tried to scrutinize different reports related to the harmful effects of SARS-CoV-2 on patients with asthma and COPD, as well as the possible therapeutic effects of stem cells in the alleviation of post-COVID-19 complications. Video abstract.


Subject(s)
Asthma , COVID-19 , Pulmonary Disease, Chronic Obstructive , Humans , SARS-CoV-2 , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/complications , Asthma/drug therapy
14.
Curr Top Microbiol Immunol ; 436: 437-466, 2022.
Article in English | MEDLINE | ID: covidwho-2075205

ABSTRACT

A number of different experimental models using both non-selective and selective PI3K inhibitors have shown that many pathogenic steps of respiratory disorders, such as bronchial asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic Pulmonary Fibrosis (IPF), Acute Respiratory Distress Syndrome (ARDS) and Lung Cancer (LC) are, at least in part, regulated by the PI3K signaling pathway, suggesting that the inhibition of PI3K could represent an ideal therapeutic target for the treatment of respiratory diseases. This chapter summarizes the current state of the therapeutic strategies aimed to exploit the inhibition of PI3K in this context. In animal models of asthma, selective δ and γ inhibitors have shown to be effective, and when administered by inhalation, reasonably safe. Nevertheless, very few clinical trials have been performed so far. The efficacy of current traditional therapies for allergic bronchial asthma has likely diminished the need for new alternative treatments. Surprisingly, in COPD, where instead there is an urgent need for new and more effective therapeutic approaches, the number of clinical studies is still low and not capable yet, with the exception for an acceptable safety profile, to show a significant improvement of clinical outcomes. In IPF, a disease with a disappointing prognosis, PI3K inhibitors have been bound to a FAP ligand with the aim to selectively target myofibroblasts, showing to significantly reduce collagen production and the development of lung fibrosis in an animal model of lung fibrosis. Due to its role in cell activation and cell replication, the PI3K pathway is obviously largely involved in lung cancer. Several studies, currently ongoing, are testing the effect of PI3K inhibitors mainly in NSCLC. Some evidence in the treatment of cancer patients suggests the possibility that PI3K inhibitors may enhance the response to conventional treatment. The involvement of PI3Kδ in the modulation of airway neutrophil recruitment and bronchial epithelial functional alterations also suggest a potential role in the treatment of ARDS, but at the current state the ongoing trials are aimed to the treatment of ARDS in COVID-19 patients. In general, few clinical trials investigating PI3K inhibitors in respiratory disorders have been performed so far. This relatively new approach of treatment is just at its beginning and certainly needs further efforts and additional studies.


Subject(s)
Asthma , COVID-19 , Idiopathic Pulmonary Fibrosis , Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Respiratory Distress Syndrome , Animals , Asthma/drug therapy , Collagen/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Ligands , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory Distress Syndrome/drug therapy
15.
N Engl J Med ; 387(13): 1173-1184, 2022 09 29.
Article in English | MEDLINE | ID: covidwho-2050642

ABSTRACT

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).


Subject(s)
Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Adrenergic beta-2 Receptor Agonists/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bronchodilator Agents/therapeutic use , Forced Expiratory Volume , Glucocorticoids/therapeutic use , Glycopyrrolate , Humans , Lung , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Tobacco/adverse effects , Treatment Outcome
16.
Am J Respir Crit Care Med ; 206(6): 712-729, 2022 09 15.
Article in English | MEDLINE | ID: covidwho-2038405

ABSTRACT

Rationale: Patients with chronic obstructive pulmonary disease (COPD) develop more severe coronavirus disease (COVID-19); however, it is unclear whether they are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and what mechanisms are responsible for severe disease. Objectives: To determine whether SARS-CoV-2 inoculated primary bronchial epithelial cells (pBECs) from patients with COPD support greater infection and elucidate the effects and mechanisms involved. Methods: We performed single-cell RNA sequencing analysis on differentiated pBECs from healthy subjects and patients with COPD 7 days after SARS-CoV-2 inoculation. We correlated changes with viral titers, proinflammatory responses, and IFN production. Measurements and Main Results: Single-cell RNA sequencing revealed that COPD pBECs had 24-fold greater infection than healthy cells, which was supported by plaque assays. Club/goblet and basal cells were the predominant populations infected and expressed mRNAs involved in viral replication. Proteases involved in SARS-CoV-2 entry/infection (TMPRSS2 and CTSB) were increased, and protease inhibitors (serpins) were downregulated more so in COPD. Inflammatory cytokines linked to COPD exacerbations and severe COVID-19 were increased, whereas IFN responses were blunted. Coexpression analysis revealed a prominent population of club/goblet cells with high type 1/2 IFN responses that were important drivers of immune responses to infection in both healthy and COPD pBECs. Therapeutic inhibition of proteases and inflammatory imbalances reduced viral titers and cytokine responses, particularly in COPD pBECs. Conclusions: COPD pBECs are more susceptible to SARS-CoV-2 infection because of increases in coreceptor expression and protease imbalances and have greater inflammatory responses. A prominent cluster of IFN-responsive club/goblet cells emerges during infection, which may be important drivers of immunity. Therapeutic interventions suppress SARS-CoV-2 replication and consequent inflammation.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Serpins , Cytokines , Epithelial Cells , Humans , Peptide Hydrolases , Pulmonary Disease, Chronic Obstructive/drug therapy , SARS-CoV-2 , Sequence Analysis, RNA , Serpins/pharmacology , Serpins/therapeutic use
17.
Adv Ther ; 39(11): 5216-5228, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2035373

ABSTRACT

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma are treatable but greatly underdiagnosed disorders. Telemedicine made it possible to continue diagnosis, follow-up visits and treatment modifications during the COVID-19 pandemic. The present study describes the management of patients with COPD and asthma, and their treatments during the pandemic from the pulmonologist's perspective. METHODS: NEUMOBIAL was an ecological study with aggregated data. A total of 279 Spanish pulmonologists answered a 60-question survey about their last 10 patients, focused on the characterisation and changes in visits and treatments during the pandemic. RESULTS: Most pulmonologists (72.0%) considered that the pandemic negatively altered the diagnosis and follow-up of patients with asthma or COPD. Diagnostic tests were reduced during the pandemic, mainly because they were not recommended by pulmonologists (68.1% and 72.7% in the case of COPD and asthma tests, respectively). Moreover, 17.3% of the COPD and 19.1% of the asthma visits were remote visits. According to pulmonologists, low adherence to treatment was mainly due to a lack of patient knowledge about their disease (75.3% and 81.7% in COPD and asthma, respectively). Other factors that also influenced adherence were inadequate use of the inhaler (59.5% for COPD and 57.7% for asthma) and a lack of knowledge about the device (57.3% for COPD and 57.7% for asthma). Pulmonologists chose Zonda® for COPD because of the ease of use of the device (73.1%) and the ability to check whether the entire dose was inhaled (69.5%). For asthma, Spiromax® was chosen because of the ease of use of the device (85.7%) and the possibility of using a single device for maintenance and reliever treatment (82.4%). CONCLUSION: According to pulmonologists, during the pandemic, treatments for COPD and asthma were mainly chosen on the basis of their ease of use; treatment adherence was good; and the number of remote visits increased.


Subject(s)
Asthma , COVID-19 , Pulmonary Disease, Chronic Obstructive , Administration, Inhalation , Asthma/drug therapy , Humans , Pandemics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonologists
18.
Inflammopharmacology ; 30(5): 1503-1516, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1982229

ABSTRACT

The Covid-19, a threatening pandemic, was originated from China in December 2019 and spread quickly to all over the world. The pathogenesis of coronavirus is linked with the disproportionate response of the immune system. This involves the systemic inflammatory reaction which is characterized by marked pro-inflammatory cytokine release commonly known as cytokine release storm (CRS). The pro inflammatory cytokines are involved in cascade of pulmonary inflammation, hyper coagulation and thrombosis which may be lethal for the individual. That's why, it is very important to have understanding of pro inflammatory cytokines and their pathological role in SARS-CoV-2. The pathogenesis of Covid is not the same in every individual, it can vary due to the presence of pre-existing comorbidities like suffering from already an inflammatory disease such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), an immune-compromised patients suffering from Diabetes Mellitus (DM) and Tuberculosis (TB) are more vulnerable morbidity and complications following COVID-19. This review is particularly related to COVID-19 patients having comorbidity of other inflammatory diseases. We have discussed the brief pathogenesis of COVID-19 and cytokines release storm with reference to other co-morbidities including RA, IBD, COPD, DM and TB. The available therapeutic regimens for COVID-19 including cytokine inhibitors, anti-viral, anti-biotic, bronchodilators, JAK- inhibitors, immunomodulators and anti-fibrotic agents have also been discussed briefly. Moreover, newly emerging medicines in the clinical trials have also been discussed which are found to be effective in treating Covid-19.


Subject(s)
COVID-19 Drug Treatment , Inflammatory Bowel Diseases , Pulmonary Disease, Chronic Obstructive , Bronchodilator Agents/therapeutic use , Comorbidity , Cytokine Release Syndrome/drug therapy , Cytokines , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , SARS-CoV-2
19.
Wiad Lek ; 75(6): 1486-1491, 2022.
Article in English | MEDLINE | ID: covidwho-1975856

ABSTRACT

OBJECTIVE: The aim: The purpose of the study is to increase the efficacy of сomprehensive treatment in elderly patients with COPD , who have suffered of coronavirus disease-COVID-19 in the last 3-6 months, by using nebulizer therapy with N-acetylcysteine and 3% hypertonic sodium chloride solution (Flu-Acyl broncho) and the drug glycine, to correct psychosomatic disorders. PATIENTS AND METHODS: Materials and methods: Under our supervision there were 60 elderly patients with COPD gr D, who underwent Covid 19 in the last 3-6 months, were under observation. The average age was 66.3±2.1 years. Рatients of the main and control groups were prescribed complex basic therapy. However, mucolytic therapy was administered to patients in the main group using combined drug - N-acetylcysteine and 3% hypertonic sodium chloride solution through a 5.0 №10 nebulizer. For the treatment of astheno-neurotic disorders of postcovidal syndrome was prescribed glycine 100 mg 2 times a day for 10 days. Subsequently, Flu-Acyl broncho through a nebulizer at 5.0 No.10, and glycised was used in courses once a day for 10 days per month. Patients in the control group were prescribed acetylcysteine 200 mg 3 times a day N10. RESULTS: Results: The results of observation for 6 months showed that in patients of the main group, recurrence of the disease was not observed. whereas in patients of the control group in 6 patients (20%). CONCLUSION: Conclusions: Comprehensive treatment of elderly patients with comorbid pathology - COPD group D and postcovidal syndrome, with the additional use of nebulizer delivery of the combined drug - N-acetylcysteine and 3% hypertonic sodium chloride solution in combination with the sedative drug glycine, promotes improving the quality of life in patients, reducing the duration of treatment, prevents recurrence and progression of COPD.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Pulmonary Disease, Chronic Obstructive , Acetylcysteine/therapeutic use , Aged , COVID-19/complications , Glycine/therapeutic use , Humans , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , Sodium Chloride
20.
Indian J Tuberc ; 69 Suppl 1: S1-S191, 2022.
Article in English | MEDLINE | ID: covidwho-1926544

ABSTRACT

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Child , Humans , Aged , Pandemics , Bronchodilator Agents/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Health Personnel
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