Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

Background Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment. Methods We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (P<5x10-8) were fine-mapped and putative causal genes identified by gene expression analysis. GWAS of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease amongst the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWAS). Findings From a GWAS of 9,714 cases and 48,471 controls, we identified six novel genome-wide significant signals for chronic sputum production including the Human Leukocyte Antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and the FUT2 locus. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino-acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations. Interpretation Novel signals at the FUT2 and mucin loci highlight mucin flucosylation as a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.

A Literature Review in Understanding the Physio-Pathological Facet of COVID-19

In December 2019, a novel coronavirus, now named as SARS-CoV-2, caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. The disease caused by this virus was termed as COVID-19 and is transmittable between humans that has caused a pandemic worldwide. An early clinical report showed that fever, cough, fatigue, sputum production, and myalgia were initial symptoms, with the development of pneumonia as the disease progressed. COVID-19 basically involved the pulmonary system at the onset, thereby involving the other organs like gastrointestinal system, cardiovascular System and nervous system is based on virulence. Increases in the level of serum liver enzymes D-dimer, cardiac troponin I, and creatinine have been observed in severely ill patients, indicating that multiple organ failure had occurred in these cases. Here, we review the current knowledge about this disease in relation to its various aspects and make comparison systemic-wise for better understanding of the systemic physio pathological aspect of Covid-19 that may help in contributing towards finding the solution that is needed at present.

Clinical Characteristics of COVID-19 Infection

The typical clinical symptoms of the patients who suffered from the novel viral pneumonia were fever, cough, and myalgia or fatigue with abnormal chest CT, and the less common symptoms were sputum production, headache, hemoptysis, and diarrhea. This new infectious agent is more likely to affect older males to cause severe respiratory diseases. Major risk factors for severe illness and mortality from COVID-19 are age, comorbidities such as: heart disease, hypertension, prior stroke, diabetes, chronic lung disease, and chronic kidney disease and associated with adverse outcomes. Loss of taste and smell preceding the onset of respiratory symptoms has been reported.

Tracheobronchoplasty and Diaphragmatic Plication under VV ECMO for Combined ECAC and Diaphragmatic Paralysis

The coexistence of expiratory central airway collapse and diaphragmatic paralysis presents a diagnostic and treatment challenge. Both entities are underrecognized causes of dyspnea, cough, sputum production, and orthopnea. Optimal treatment must be individualized and is best achieved by a multidisciplinary team. We present a case of a patient with profound functional impairment from dyspnea and hypoxemia due to expiratory central airway collapse, complicated by bronchiectasis from recurrent respiratory infections, and diaphragmatic paralysis.

Novel method to select meaningful outcomes for evaluation in clinical trials

BackgroundA standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF).MethodsWe conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process.ResultsThe 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms.ConclusionsThis proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.

Association between initial symptoms and subsequent hospitalization in outpatients with COVID-19: a cohort study

Background: Most individuals with coronavirus disease 2019 (COVID-19) experience mild symptoms and are managed in the outpatient setting. The aim of this study was to determine whether self-reported symptoms at the time of diagnosis can identify patients at risk of clinical deterioration. Methods: This was a retrospective cohort study of 671 outpatients with laboratory-confirmed COVID-19 diagnosed in Toronto between March 1 and October 16, 2020. We examined the association between patients’ baseline characteristics and self-reported symptoms at the time of diagnosis and the risk of subsequent hospitalization. Results: Of 671 participants, 26 (3.9%) required hospitalization. Individuals aged 65 years or older were more likely to require hospitalization (OR = 5.29, 95% CI 2.19 to 12.77), whereas those without medical comorbidities were unlikely to be hospitalized (OR = 0.02, 95% CI 0.00 to 0.17). After adjusting for age and presence of comorbidities, sputum production (adjusted OR [aOR] = 5.01, 95% CI 1.97 to 12.75), arthralgias (aOR = 4.82, 95% CI 1.85 to 12.53), diarrhea (aOR = 4.56, 95% CI 1.82 to 11.42), fever (aOR = 3.64, 95% CI 1.50 to 8.82), chills (aOR = 3.62, 95% CI 1.54 to 8.50), and fatigue (aOR = 2.59, 95% CI 1.04 to 6.47) were associated with subsequent hospitalization. Conclusions: Early assessment of symptoms among outpatients with COVID-19 can help identify individuals at risk of clinical deterioration. Additional studies are needed to determine whether more intense follow-up and early intervention among high-risk individuals can alter the clinical trajectory of and outcomes among outpatients with COVID-19.

HRCT in Bronchiectasis

In patients with bronchiectasis, a high-resolution CT scan (HRCT) and its score play a significant role in identifying pathological alterations and pulmonary functional impairment. A total of 50 cases were studied. All the cases presenting with the features suggestive of bronchiectasis were screened clinically . 8 out of 50 patients underwent surgical resection of affected lobes. The rest was handled with caution. The primary condition, lung malignancy, claimed the life of one patient. CT can be used to quickly confirm suspected bronchiectasis due to its increased specificity. Confirmation by CT is useful in the management of patients with chronic cough and sputum production who are suspected of having bronchiectasis but for whom surgery is not an option due to age or poor lung function. In some cases, where surgery appears to be a viable option, unmistakable evidence of bilateral bronchiectasis on CT would rule out such treatment without the requirement for bronchography.

Prolonged Slow Expiration (PSE) and Prone Position Intervention in Children : A Literature Review

<p>Nursing interventions to reduce the impact of respiratory problems in children aged &lt; 24 months in inpatient rooms are not only a science but also an art. This study aimed to determine the effectiveness of Prolonged Slow Expiration (PSE) and prone position in improving respiratory function in hospitalized children aged &lt; 24 months with respiratory distress in inpatient rooms. This literature review examined thirteen peer-reviewed journals based on inclusion criteria. The results of the review showed that PSE and prone position can reduce the respiratory frequency, maintain the neuromechanical diaphragm, and increase tidal volume. PSE was more effective at lowering the bronchiolitis scale score, preventing the child from experiencing moderate to severe respiratory distress, and decreasing relative sputum production. The prone position is more effective in increasing SaO2 even when using mechanical ventilation (MV), can increase maximal inspiratory pressure (MIP) and tissue oxygenation index (TOI), provides sleeping comfort, improves cardiorespiratory function, reduces moderate to severe respiratory distress, and can perform intubation. It can be concluded that PSE is a safe and easy therapy to administer to mild respiratory distress patients but has not a significant effect on children &lt; 24 months with moderate to severe respiratory distress in inpatient rooms.</p>

Prognosis and treatment of 46 Chinese pediatric cystic fibrosis patients

Background Since public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China. Method Treatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test. Results Of 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5–62 months and 0.5–48 months, respectively, and triggered no obvious adverse reactions. Conclusion No obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.

PENGARUH LATIHAN AEROBIK TERHADAP KUALITAS HIDUP PASIEN PENYAKIT PARU OBSTRUKTIF KRONIK

Patients with COPD experience a fundamental inability to breathe in the form of shortness of breath, chronic cough, chronic sputum production, and limited activity. Aerobic exercise for COPD sufferers aims to reduce symptoms, improve quality of life and increase daily activities. This study aims to determine the effect of aerobic exercise on the quality of life of COPD patients. This research is a quantitative study using a quasi-experimental design with a pretest-posttest research design, using the sampling technique is purposive sampling with 44 respondents. Retrieval of data using a quality of life questionnaire for COPD patients. The results of the paired t test showed a value of p <0.000, which means that p <0.05, this shows in general that aerobic exercise has an effect on the quality of life of COPD patients. COPD sufferers who routinely do aerobic exercise regularly will increase their perfusion so that tissue needs can be fulfilled and COPD symptoms, especially shortness of breath, will decrease.