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In a placebo-controlled, phase 2–3 trial, one dose of mRNA-1345 led to a lower incidence of RSV disease among adults 60 years of age or older. Solicited local and systemic adverse reactions occurred more often with the vaccine.

Previous evidence suggests an association between gastroesophageal reflux disease and chronic respiratory disease in children. Despite antisecretory antacid therapy, respiratory symptoms often persist supporting a role for nonacid reflux. The aim of this study was to determine whether nonacid reflux occurs in children with chronic respiratory disease. Twenty-eight children (mean age: 6.5 +/- 5.6 yr) with persistent respiratory symptoms on antacid medications underwent 24 h pH/multichannel intraluminal impedance (pH/MII) recording. The symptom index (SI) and the symptom sensitivity index (SSI) were calculated for each patient. Logistic regression was performed to determine which reflux characteristics were associated with a high degree of symptom correlation present during the occurrence of symptoms. A total of 1,822 reflux episodes were detected by pH/MII, 45% of which were nonacidic. The mean SI increased using pH/MII (35.7 +/- 28.5) compared to pH probe alone (14.6 +/- 18.9; p= 0.002); no differences in the mean SSI using pH/MII compared to pH probe alone were identified. Significantly more patients had a positive SI using pH/MII than pH probe alone (p= 0.035); there was no difference in the number of patients with a positive SSI using pH/MII compared to pH probe alone. Multivariate analysis revealed that symptoms occurred more frequently when the reflux was nonacidic, mixed, and full column. Also, younger children were more likely to have the simultaneous occurrence of symptoms and reflux. Nonacid reflux may be an important predictor of respiratory symptoms. pH/MII provided important information in the evaluation of children with intractable respiratory symptoms.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm³ at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm³ at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

Similar to human medicine, attempts have been made in veterinary medicine to assess the severity of respiratory disorders using methods other than respiratory function evaluation; however, such approaches remain insufficient. Medical records at a single small animal private referral center for emergency care were reviewed to identify dogs with respiratory disorders diagnosed by radiography during 2016-2019. The variables of screening test evaluated in this study included patient characteristics, physical examination, and blood test findings. The cases were also divided into Survivors, which were defined as dogs surviving over 7 days from the first consultation day, and Non-survivors, including the dogs euthanized and died naturally within 7 days from the consultation day. In univariate analysis, heart rates, body temperature, white blood count (WBC), glucose, blood urea nitrogen (BUN), phosphate and lactate were significantly different between Survivors and Non-survivors. Multiple logistic regression model with these significant variables revealed that only phosphate was associated with a poor prognosis. This study has demonstrated several parameters of physical examination and blood test, especially plasma phosphate concentration, could be related with mortality in canine respiratory disorders. Although further studies are needed, these parameters may enable more accurate assessment of the severity of respiratory disorders in dogs by combining with the conventional assessments of respiratory functions including oxygenation and ventilation.

Most of the epidemiological studies that have examined the detrimental effects of ambient hot and cold temperatures on human health have been conducted in high-income countries. In India, the limited evidence on temperature and health risks has focused mostly on the effects of heat waves and has mostly been from small scale studies. Here, we quantify heat and cold effects on mortality in India using a nationally representative study of the causes of death and daily temperature data for 2001-2013. We applied distributed-lag nonlinear models with case-crossover models to assess the effects of heat and cold on all medical causes of death for all ages from birth (n = 411,613) as well as on stroke (n = 19,753), ischaemic heart disease (IHD) (n = 40,003), and respiratory diseases (n = 23,595) among adults aged 30-69. We calculated the attributable risk fractions by mortality cause for extremely cold (0.4 to 13.8°C), moderately cold (13.8°C to cause-specific minimum mortality temperatures), moderately hot (cause-specific minimum mortality temperatures to 34.2°C), and extremely hot temperatures (34.2 to 39.7°C). We further calculated the temperature-attributable deaths using the United Nations' death estimates for India in 2015. Mortality from all medical causes, stroke, and respiratory diseases showed excess risks at moderately cold temperature and hot temperature. For all examined causes, moderately cold temperature was estimated to have higher attributable risks (6.3% [95% empirical confidence interval (eCI) 1.1 to 11.1] for all medical deaths, 27.2% [11.4 to 40.2] for stroke, 9.7% [3.7 to 15.3] for IHD, and 6.5% [3.5 to 9.2] for respiratory diseases) than extremely cold, moderately hot, and extremely hot temperatures. In 2015, 197,000 (121,000 to 259,000) deaths from stroke, IHD, and respiratory diseases at ages 30-69 years were attributable to moderately cold temperature, which was 12- and 42-fold higher than totals from extremely cold and extremely hot temperature, respectively. The main limitation of this study was the coarse spatial resolution of the temperature data, which may mask microclimate effects. Public health interventions to mitigate temperature effects need to focus not only on extremely hot temperatures but also moderately cold temperatures. Future absolute totals of temperature-related deaths are likely to depend on the large absolute numbers of people exposed to both extremely hot and moderately cold temperatures. Similar large-scale and nationally representative studies are required in other low- and middle-income countries to better understand the impact of future temperature changes on cause-specific mortality.

ObjectiveTo determine the early predictors of respiratory hospital admissions in young people with cerebral palsy (CP).DesignA 3-year prospective cohort study using linked data.PatientsChildren and young people with CP, aged 1 to 26 years.Main outcome measuresSelf-reported and carer-reported respiratory symptoms were linked to respiratory hospital admissions (as defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes) during the following 3 years.Results482 participants (including 289 males) were recruited. They were aged 1 to 26 years (mean 10 years, 10 months; SD 5 years, 11 months) at the commencement of the study, and represented all Gross Motor Function Classification Scale (GMFCS) levels. During the 3-year period, 55 (11.4%) participants had a total of 186 respiratory hospital admissions, and spent a total of 1475 days in hospital. Statistically significant risk factors for subsequent respiratory hospital admissions over 3 years in univariate analyses were GMFCS level V, at least one respiratory hospital admission in the year preceding the survey, oropharyngeal dysphagia, seizures, frequent respiratory symptoms, gastro-oesophageal reflux disease, at least two courses of antibiotics in the year preceding the survey, mealtime respiratory symptoms and nightly snoring.ConclusionsMost risk factors for respiratory hospital admissions are potentially modifiable. Early identification of oropharyngeal dysphagia and the management of seizures may help prevent serious respiratory illness. One respiratory hospital admission should trigger further evaluation and management to prevent subsequent respiratory illness.

Medical practice is built on the foundations of evidence-based medicine. Hence, the more common the clinical intervention, the more comprehensive the evidence on which that intervention should be based. Although the widespread adoption of a national early warning score in the UK has led to improvements in the delivery of care, it should be considered as providing a foundation that can be refined and developed, and there is still a need for critical reflection and evaluation of early warning scores, particularly for individuals with chronic respiratory disease, in order to optimise patient monitoring, predict deterioration and guide intervention.

Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.Lung disease: suppressing immune protein could reduce fibrosisAn immune protein that contributes to fibrosis, inflammation, and cellular dysfunction in the airways should be a target of therapies for severe lung diseases. Previously thought of as protective, the cytokine interleukin-11 (IL-11) evolved as part of the body’s immune system, and is highly expressed in the parenchyma and stroma of the diseased lung. Sebastian Schäfer at National Heart Centre Singapore and co-workers review recent research evidence indicating that IL-11 signaling is centrally important in pathological processes including the dysfunction of epithelial cells, inflammation of connective tissue, and the activation of cells that induce fibrotic scarring. Antibody therapies targeting IL-11 can reduce pulmonary fibrosis and inflammation in mice. Pharmacological companies may soon begin clinical trials of anti-IL-11 therapies on patients with idiopathic pulmonary fibrosis, a severe lung disease sharing several risk factors with COVID-19.

Respiratory disease and, specifically, pneumonia, is the major cause of mortality and morbidity in young children. Diagnosis of both pneumonia and asthma in primary care rests principally on clinical signs, history taking, and bronchodilator responsiveness. This study aimed to describe clinical practices in diverse global primary care settings concerning differential diagnosis of respiratory disease in young children, especially between pneumonia and asthma. Health professionals in Greece, Kyrgyzstan, Vietnam, and Uganda were observed during consultations with children aged 2-59 months, presenting with cough and/or difficult breathing. Data were analyzed descriptively and included consultation duration, practices, diagnoses and availability/use of medications and equipment. The study is part of the European Horizon 2020 FRESH AIR project. In total, 771 consultations by 127 health professionals at 74 facilities in the four countries were observed. Consultations were shorter in Vietnam and Uganda (3 to 4 minutes) compared to Greece and Kyrgyzstan (15 to 20 minutes). History taking was most comprehensive in Greece. Clinical examination was more comprehensive in Vietnam and Kyrgyzstan and less in Uganda. Viral upper respiratory tract infections were the most common diagnoses (41.7% to 67%). Pneumonia was diagnosed frequently in Uganda (16.3% of children), and rarely in other countries (0.8% to 2.9%). Asthma diagnosis was rare (0% to 2.8%). Antibiotics were prescribed frequently in all countries (32% to 69%). Short acting β-agonist trials were seldom available and used during consultations in Kyrgyzstan (0%) and Uganda (1.8%), and often in Greece (38.9%) and Vietnam (12.6%). Duration and comprehensiveness of clinical consultations observed in this study seemed insufficient to guide respiratory diagnosis in young children. Appropriate treatment options may further not be available in certain studied settings. Actions aiming at educating and raising professional awareness, along with developing easy-to-use tools to support diagnosis and a general strengthening of health systems are important goals.