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Context: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess., Objective: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients., Methods: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels., Results: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L., Conclusion: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Congenital lung and lower airway abnormalities are rare, but they are an important differential diagnosis in children with respiratory diseases, especially if the disease is recurrent or does not resolve. The factors determining the time of presentation of congenital airway pathologies include the severity of narrowing, association with other lesions and the presence or absence of congenital heart disease (CHD). Bronchoscopy is required in these cases to assess the airway early after birth or when intubation and ventilation are difficult or not possible. Many of these conditions have associated abnormalities that must be diagnosed early, as this determines surgical interventions. It may be necessary to combine imaging and bronchoscopy findings in these children to determine the correct diagnosis as well as in operative management. Endoscopic interventional procedures may be needed in many of these conditions, ranging from intubation to balloon dilatations and aortopexy. This review will describe the bronchoscopic findings in children with congenital lung and lower airway abnormalities, illustrate how bronchoscopy can be used for diagnosis and highlight the role of interventional bronchoscopy in the management of these conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It is unclear which factor Xa (FXa) inhibitors are associated with higher bleeding risk in patients with respiratory diseases, and there are no studies on the association between prothrombin time-international normalized ratio (PT-INR) and bleeding risk. We conducted a retrospective cohort study comparing 1-year-outcomes and PT-INR between patients with respiratory diseases treated with rivaroxaban (R group, n = 82) or edoxaban (E group, n = 138) for atrial fibrillation or venous thromboembolism from 2013 to 2021. The most frequent event of all bleeding discontinuations was respiratory bleeding in both groups (7.3 and 4.3%, respectively). The cumulative incidence of bleeding discontinuation was significantly higher in the R group (25.6%) than in the E group (14.4%) (hazard ratio [HR], 2.29; 95% confidence interval [CI] 1.13-4.64; P = 0.023). PT-INR after initiation of therapy significantly increased and was higher in the R group than in the E group (median value, 1.4 and 1.2, respectively; P < 0.001). Multivariate analysis using Cox proportional hazards and Fine-Gray models revealed that PT-INR after initiation of therapy was an independent risk factor of bleeding discontinuation events (HR = 4.37, 95% CI 2.57-7.41: P < 0.001). Respiratory bleeding occasionally occurs in patients receiving FXa inhibitors, and monitoring the PT-INR may need to ensure safety., (© 2024. The Author(s).)

CYP2A6, a genetically variable enzyme, inactivates nicotine, activates carcinogens, and metabolizes many pharmaceuticals. Variation in CYP2A6 influences smoking behaviors and tobacco-related disease risk. This phenome-wide association study examined associations between a reconstructed version of our weighted genetic risk score (wGRS) for CYP2A6 activity with diseases in the UK Biobank (N = 395 887). Causal effects of phenotypic CYP2A6 activity (measured as the nicotine metabolite ratio: 3'-hydroxycotinine/cotinine) on the phenome-wide significant (PWS) signals were then estimated in two-sample Mendelian Randomization using the wGRS as the instrument. Time-to-diagnosis age was compared between faster versus slower CYP2A6 metabolizers for the PWS signals in survival analyses. In the total sample, six PWS signals were identified: two lung cancers and four obstructive respiratory diseases PheCodes, where faster CYP2A6 activity was associated with greater disease risk (Ps < 1 × 10-6). A significant CYP2A6-by-smoking status interaction was found (Psinteraction < 0.05); in current smokers, the same six PWS signals were found as identified in the total group, whereas no PWS signals were found in former or never smokers. In the total sample and current smokers, CYP2A6 activity causal estimates on the six PWS signals were significant in Mendelian Randomization (Ps < 5 × 10-5). Additionally, faster CYP2A6 metabolizer status was associated with younger age of disease diagnosis for the six PWS signals (Ps < 5 × 10-4, in current smokers). These findings support a role for faster CYP2A6 activity as a causal risk factor for lung cancers and obstructive respiratory diseases among current smokers, and a younger onset of these diseases. This research utilized the UK Biobank Resource., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

With the change in global environment, respiratory disorders are becoming more threatening to the health of people all over the world. These diseases are closely linked to performance of immune system. Within the innate arm of immune system, Neutrophils are an important moiety to serve as an immune defense barrier. They are one of the first cells recruited to the site of infection and plays a critical role in pathogenesis of various pulmonary diseases. It is established that the migration and activation of neutrophils can lead to inflammation either directly or indirectly and this inflammation caused is very crucial for the clearance of pathogens and resolution of infection. However, the immunopathological mechanisms involved to carry out the same is very complex and not well understood. Despite there being studies concentrating on the role of neutrophils in multiple respiratory diseases, there is still a long way to go in order to completely understand the complexity of the participation of neutrophils and mechanisms involved in the development of these respiratory diseases. In the present article, we have reviewed the literature to comprehensively provide an insight in the current development and advancements about the role of neutrophils in infectious respiratory disorders including viral respiratory disorders such as Coronavirus disease (COVID-19) and bacterial pulmonary disorders with a focused review on pulmonary tuberculosis as well as in noninfectious disorders like Chronic obstructive pulmonary disease (COPD) and asthma. Also, future directions into research and therapeutic targets have been discussed for further exploration.

Background: This study aims to accurately estimate influenza-associated deaths in Poland and their certified cause of death, due to significant discrepancies between official numbers and expected impact., Methods: Excess influenza-associated mortality in Poland from 2000 to 2019 was calculated using Seasonal-Trend Decomposition Procedure based on LOESS (STL), which can detect non-linear trends and non-sinusoidal cycles. Excess mortality was then used as an explanatory variable in a model predicting monthly fluctuations of officially recorded causes of death from 2010 to 2019., Results: A total of 142,000 conservative estimates of influenza-associated deaths were identified, representing 1.86% of overall mortality. Only 0.61% of influenza-associated deaths were officially recorded as influenza. Nearly half of certified influenza deaths were attributed to the seasonal baseline mortality, potentially doubling estimated impact based solely on influenza peaks. Influenza-associated deaths were frequently recorded as respiratory diseases (24.36%), with majority attributed to underlying conditions such as cardiovascular diseases (45.31%), cancer (9.06%), or diabetes (2.66%). Influenza-associated deaths were more commonly certified as nervous system diseases (1.84%) or mental disorders (1.04%), rather than influenza itself. There was a noticeable impact of influenza on secondary infections, such as meningococcal and gastrointestinal infections., Conclusion: These findings highlight the importance of improved estimation for informing public health policy decisions., Competing Interests: We declare no competing interests., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

BACKGROUND: Respiratory diseases of infectious, allergic, neoplastic or degenerative origin are due to the interaction of environmental and occupational risk factors, individual susceptibility and other co-factors and comorbidities. Asthma and other respiratory pathologies can be worsened by climate change and exposure to other agents in occupational environments. METHODS: PubMed and Scopus, and several websites on public and occupational health were queried to find publications and documents on work-related respiratory diseases, asthma, rhinitis, chronic obstructive pulmonary disease (COPD), pneumoconiosis and allergic alveolitis in association with climate change. RESULTS: Most of the retrieved articles concerned asthma (75 in Scopus), while the other topics were less frequently covered in the scientific literature, with a maximum of 29 papers for rhinitis and 23 for COPD. The most important terms highlighted by the word clouds were 'health', 'air', 'pollution', and, only for asthma and rhinitis, 'pollen' and 'allergic/allergy'. Website data on public and occupational health, and climate change were reported. CONCLUSIONS: Assessment and management of respiratory diseases that recognise occupational exposures should be improved, and more research into integrated approaches should be favoured. Health surveillance practices for workers exposed to agents that cause respiratory diseases should be implemented. The development of biomarkers of exposure, effect and susceptibility needs further study.

Background: The prospective associations of preserved ratio impaired spirometry (PRISm) with new-onset macrovascular and microvascular complications and mortality among individuals with type 2 diabetes (T2D) and whether PRISm enhances the prediction ability of an established office-based risk score remain to be elucidated., Research Question: Can PRISm be used as a predictor of poor prognosis in individuals with T2D?, Study Design and Methods: We included 20,047 study participants with T2D and complete data on spirometry at recruitment from the UK Biobank cohort. Multivariable Cox proportional hazards models were used to assess the associations of baseline PRISm (FEV 1 to FVC ratio, ≥ 0.70; FEV 1 , < 80% predicted) with subsequent risks of incident stroke (any type), ischemic stroke, myocardial infarction, unstable angina, coronary heart disease, diabetic retinopathy, diabetic kidney disease, all-cause mortality, cardiovascular mortality, and respiratory mortality., Results: For this cohort analysis, 4,521 patients (22.55% of participants with T2D) showed comorbid PRISm at baseline. Over a median follow-up of 11.52 to 11.87 years, patients with T2D with PRISm at baseline showed higher risks than those with normal spirometry findings of various T2D complications developing and mortality; the adjusted hazard ratios for PRISm were 1.413 (95% CI, 1.187-1.681) for stroke (any type), 1.382 (95% CI, 1.129-1.690) for ischemic stroke, 1.253 (95% CI, 1.045-1.503) for myocardial infarction, 1.206 (95% CI, 1.086-1.339) for coronary heart disease, 1.311 (95% CI, 1.141-1.506) for diabetic retinopathy, 1.384 (95% CI, 1.190-1.610) for diabetic kidney disease, 1.337 (95% CI, 1.213-1.474) for all-cause mortality, 1.597 (95% CI, 1.296-1.967) for cardiovascular mortality, and 1.559 (95% CI, 1.189-2.044) for respiratory mortality, respectively. The addition of PRISm significantly improved the reclassification ability, based on the net reclassification index, of an office-based risk score by 15.53% (95% CI, 10.14%-19.63%) to 33.60% (95% CI, 20.90%-45.79%)., Interpretation: Individuals with T2D with comorbid PRISm, accounting for a considerable proportion of the population with T2D, showed significantly increased risks of adverse macrovascular and microvascular complications and mortality., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: Lung ultrasound (LUS) is a useful and radiation-free diagnostic tool for predicting bronchopulmonary dysplasia, which is a risk factor for late respiratory disease. However, data on the relationship of LUS with late respiratory disease was scarce. This study aims to determine whether LUS is associated with late respiratory disease during early childhood., Methods: This prospective cohort study enrolled preterm infants born before 32 weeks of gestation. LUS was performed at 36 weeks' postmenstrual age. The predictive values of a modified lung ultrasound (mLUS) score based on eight standard sections were assessed to predict late respiratory disease, defined as a physician diagnosis of bronchopulmonary dysplasia deterioration, asthma, reactive airway disease, bronchiolitis, pneumonia, or respiratory-related hospitalization during the first 2 years of life., Results: A total of 94 infants completed follow-up, of whom 74.5% met the late respiratory disease criteria. The mLUS scores were significantly associated with late respiratory disease (adjusted odds ratio: 1.23, CI: 1.10-1.38, p < 0.001). The mLUS scores also well predicted late respiratory disease (AUC = 0.820, 95% CI: 0.733-0.907). These scores were superior to the classic lung ultrasound score (p = 0.02) and as accurate as the modified NICHD-defined bronchopulmonary dysplasia classification (p = 0.91). A mLUS score ≥14 was the optimal cutoff point for predicting late respiratory disease., Conclusion: The modified lung ultrasound score correlates significantly with late respiratory disease and well predicts it in preterm infants during the first 2 years of life., (© 2023 Wiley Periodicals LLC.)

Myasthenia gravis (MG) is characterized by muscle weakness caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction and impair acetylcholine receptor function. Weakness of respiratory muscles represents the most severe MG manifestation, and 10-15% of all patients experience an MG crisis with the need of mechanical ventilatory support at least once in their life. MG patients with respiratory muscle weakness need active immunosuppressive drug treatment long term, and they need regular specialist follow-up. Comorbidities affecting respiratory function need attention and optimal treatment. Respiratory tract infections can lead to MG exacerbations and precipitate an MG crisis. Intravenous immunoglobulin and plasma exchange are the core treatments for severe MG exacerbations. High-dose corticosteroids, complement inhibitors, and FcRn blockers represent fast-acting treatments that are effective in most MG patients. Neonatal myasthenia is a transient condition with muscle weakness in the newborn caused by mother's muscle antibodies. In rare cases, treatment of respiratory muscle weakness in the baby is required., (© 2023. The Author(s).)

Background and Objectives : Pulmonary hypertension (PH) secondary to left-sided valvular heart disease is associated with poor cardiac surgical outcome compared with patients without PH. Our objective was to investigate the prognostic factors of surgical outcome in patients with PH undergoing mitral valve (MV) and tricuspid valve (TV) surgery, in order to risk stratify their management. Materials and Methods : This is a retrospective observational study on patients with PH who underwent MV and TV surgery from 2011 to 2019. The primary outcome was all-cause mortality. The secondary outcomes were post-op respiratory and renal complications, length of intensive care unit stay and length of hospital stay. Results : Seventy-six patients were included in this study. The all-cause mortality was 13% ( n = 10), with mean survival of 92.6 months. Among the patients, 9.2% ( n = 7) had post-op renal failure requiring renal replacement therapy and 6.6% ( n = 5) had post-op respiratory failure requiring intubation. Univariate analysis demonstrated that pre-operative left ventricular ejection fraction (LVEF), peak systolic tissue velocity at the tricuspid annulus (S') and etiology of MV disease were associated with respiratory and renal failure. Tricuspid annular plane systolic excursion (TAPSE) was associated with respiratory failure only. S', type of operation, LVEF, urgency of surgery, and etiology of MV disease were found to be predictive of mortality. After excluding redo mitral surgery, all statistically significant findings remain unchanged, with the addition of right ventricular (RV) size being associated with respiratory failure. In the subgroup analysis of routine cases ( n = 56), patients with primary mitral regurgitation who underwent mitral valve repair had better survival outcome. Conclusions : Urgency of surgery, etiology of MV disease, type of operation (replacement or repair), S' and pre-op LVEF are prognostic indicators in this small cohort of patients with PH undergoing MV and TV surgery. A larger prospective study is warranted to validate our findings.

Aim: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles., Materials and Methods: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings., Results: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors., Conclusions: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: The objective of the present narrative review was to evaluate the evidence of a possible association between periodontitis and COVID-19, and its biological plausibility, using as models the potential associations with cardiovascular diseases, diabetes, and some respiratory diseases., Methods: A recent systematic review was used as main reference to explore the associations of periodontitis with different respiratory diseases, including COVID-19, following two focussed questions: a PECOS question, aimed to explore epidemiological evidence, and a PICOS question, designed to explore the evidence derived from intervention studies. In addition to that evidence, other relevant scientific documents, including consensus papers, were carefully selected and appraised., Findings: Convincing evidence was found to support the association of periodontitis and cardiovascular diseases, diabetes, and some respiratory diseases. The biological plausibility behind those associations is based on four factors: (1) bacteraemia of oral bacteria and periodontal pathogens, (2) increased systemic inflammation, (3) common genetic factors, and (4) common environmental risk factors. Limited initial evidence is available to support an association between periodontitis and COVID-19 complications. Among the proposed factors to explain the suggested association, a combination of the previously mentioned factors, plus additional factors related with SARS-CoV-2 characteristics and pathogenicity, has been suggested., Conclusions: Initial evidence suggests that periodontitis may be associated with a more severe COVID-19 and with a higher risk of death due to COVID-19., Clinical Relevance: Due to the possible association between periodontitis and an increased severity for COVID-19, additional efforts should be made to improve oral and periodontal health, including the promotion of oral healthy habits, such as oral hygiene., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hemosiderophages in bronchoalveolar lavage fluid (BALF) are commonly ascribed to exercise-induced pulmonary hemorrhage (EIPH). Little information exists regarding the presence of these cells in horses that perform light or no work and that are referred for respiratory problems., Objectives: Evaluate the presence of hemosiderophages in BALF of horses suspected of respiratory disease without history of or risk factors for EIPH and determine predictors of hemosiderophages in BALF in this population., Methods: Observational retrospective cross-sectional study using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Bronchoalveolar lavage fluid cytology reports of 353 horses evaluated for respiratory disease between 2012 and 2022 at the Cummings School for Veterinary Medicine were reviewed retrospectively. Horses with a history or likelihood of having performed past strenuous exercise were removed, and the remaining 91 horses were divided into hemosiderin-positive (HSD-POS) and hemosiderin-negative groups based on Perls' Prussian blue staining. Potential predictors for the presence of hemosiderophages in BALF (history, clinical evaluation, baseline lung function, airway reactivity, BALF cytology, and hemosiderin score) were compared between the 2 groups, using univariate and multivariate analyses., Results: Horses with a diagnosis of severe equine asthma (sEA; odds ratio, 11.1; 95% confidence interval, 3.2-38.5; P < .001) were significantly more likely to be HSD-POS than horses with mild-to-moderate equine asthma., Conclusions and Clinical Importance: Hemosiderophages were found in the BALF cytology in a subset of horses that perform light or no work and presented for respiratory signs; these cells were found more frequently in horses with sEA. The link between hemosiderophages and sEA highlights previously unstudied pathology associated with this common disease., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: We aimed to explore the risk factors and countermeasures of stress urinary incontinence (SUI) after mesh implantation for patients with pelvic organ prolapse (POP)., Methods: A total of 224 POP patients undergoing mesh implantation from January 2018 to December 2021 were divided into group A (n = 68, postoperative new-onset SUI) and group B (n = 156, without postoperative new-onset SUI). Their clinical data were collected, and the treatment outcomes were analyzed. The independent risk factors for postoperative new-onset SUI were determined through multivariate logistic regression analysis. A risk-scoring model was established and assessed. The patients with postoperative new-onset SUI were divided into low-, moderate- and high-risk groups using this model., Results: Mesh implantation significantly improved the pelvic floor muscle strength and function of patients. Multivariate logistic regression analysis revealed that age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration were independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation was a protective factor ( p < 0.05). The risk-scoring model was safe, reliable and practical, with high discrimination, accuracy and efficiency., Conclusions: Age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration are independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation is a protective factor. Therefore, POP patients with new-onset SUI following mesh implantation should receive more pelvic floor muscle training., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Introduction: Respiratory dysfunction in Parkinson's disease (PD) is common and associated with increased hospital admission and mortality rates. Central and peripheral mechanisms have been proposed in PD. To date no systematic review identifies the extent and type of respiratory impairments in PD compared with healthy controls., Methods: PubMed, EMBASE, CINAHL, Web of Science, Pedro, MEDLINE, Cochrane Library and OpenGrey were searched from inception to December 2021 to identify case-control studies reporting respiratory measures in PD and matched controls., Results: Thirty-nine studies met inclusion criteria, the majority with low risk of bias across Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) domains. Data permitted pooled analysis for 26 distinct respiratory measures. High-to-moderate certainty evidence of impairment in PD was identified for vital capacity (standardised mean difference [SMD] 0.75; 95% CI 0.45-1.05; p < 0.00001; I 2  = 10%), total chest wall volume (SMD 0.38; 95% CI 0.09-0.68; p = 0.01; I 2  = 0%), maximum inspiratory pressure (SMD 0.91; 95% CI 0.64-1.19; p < 0.00001; I 2  = 43%) and sniff nasal inspiratory pressure (SMD 0.58; 95% CI 0.30-0.87; p < 0.00001; I 2  = 0%). Sensitivity analysis provided high-moderate certainty evidence of impairment for forced vital capacity and forced expiratory volume in 1 s during medication ON phases and increased respiratory rate during OFF phases. Lower certainty evidence identified impairments in PD for maximum expiratory pressure, tidal volume, maximum voluntary ventilation and peak cough flow., Conclusions: Strong evidence supports a restrictive pattern with inspiratory muscle weakness in PD compared with healthy controls. Limited data for central impairment were identified with inconclusive findings., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease., Methods: In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease., Results: There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn's disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms., Conclusions: Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Medical records of 16 Japanese Black calves with respiratory signs associated with perinatal rib fracture were analyzed, retrospectively, to speculate criteria of surgical intervention for the disease. For this analysis, the severity of respiratory condition was classified into three grades: Grade 1, with no wheezing, Grade 2, with wheezing after excitement but not at rest and Grade 3, with wheezing at rest. Grade 1 (n=3) received only conservative management. Seven of Grade 2 (n=8) and all of Grade 3 (n=5) had surgical management. Clinical outcome was good in all of Grade 1, and the surgical success rate was 83% in other groups. Our result suggests that surgical intervention should be considered for cases with more the severity of Grade 2.

Background: Salivary bile acids are used to diagnose extraesophageal reflux (EER) and to evaluate the risk of reflux aspiration that is associated with respiratory diseases in dogs., Objectives: To study total bile acid (TBA) concentrations in saliva and in bronchoalveolar lavage fluid (BALF) to investigate EER and reflux aspiration in dogs with respiratory diseases and in healthy dogs., Animals:  Thirty-one West Highland White Terriers (WHWTs) with idiopathic pulmonary fibrosis (IPF), 12 dogs with inflammatory airway disease (IAD), 6 dogs with recurrent pneumonia (RP), 26 brachycephalic dogs (BD), 27 healthy WHWTs (HW), 52 healthy dogs (HD). All privately-owned dogs., Methods: Saliva and BALF were collected from dogs in each group., Results: Salivary TBA concentrations were higher in IPF (median 0.1692 μM, interquartile range [IQR] 0.1115-0.2925 μM, Cohen's d 3.4, 95% confidence interval [CI] 2.2-4.0, P < .001) and BD (0.0256 μM, IQR 0.0086-0.0417 μM, d 0.5, CI -0.1 to 1.1, P = .003) compared to HD (0 μM, IQR not quantifiable [n.q.]-0.0131 μM). Bronchoalveolar lavage fluid TBA concentrations were higher in IPF (0.0117 μM, IQR 0.0048-0.0361 μM, d 0.5, CI 0-1.1, P < .001) compared to HD (0 μM, IQR n.q.-0.0074 μM)., Conclusion and Clinical Importance: Extraesophageal reflux and reflux aspiration occur in healthy dogs and those with respiratory diseases., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Purpose: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK., Materials and Methods: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases)., Results: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p  = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p  = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p  = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p  = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p  = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p  = .25)., Conclusion: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

In the veal industry in The Netherlands, each year around 1.2 million "white" veal calves are produced on around 1100 farms. Bovine respiratory disease (BRD) causes serious health issues in these calves, also resulting in high usage of antimicrobials. To reduce antimicrobial usage, a more targeted treatment regime is needed, for which it is necessary to identify the causative agent. This study aimed at determining associations between pathogens and clinical disease, between prevalence of pathogens and BRD outbreaks, and BRD and performance. A cohort study was conducted involving ten veal farms, in which calf respiratory health was evaluated for the first 12 weeks. Whenever there was an outbreak of BRD, as determined by the farm veterinary surgeon, samples were taken from diseased and control calves through broncho-alveolar lavage. From these samples a broad spectrum of micro-organisms were isolated. Performance data were also collected. A total of 23 outbreaks happened during the 12 week study period, mostly in the first six weeks. BRD associated pathogens found were: BHV1, BPI3V, BRSV, BVDV, Pasteurella multocida, Mannheimia haemolytica, Trueperella pyogenes, Histophilus somni, Mycoplasma bovis, Mycoplasma bovirhinis and Mycoplasma dispar. For most BRD associated pathogens, there was no clear association between presence or prevalence of the micro-organisms and clinical issues. Only T. pyogenes (7.4% in healthy, 14.6% in diseased calves, p 0.013), M. bovis (37.6% and 63.2% respectively, p 0.001) and BVDV (9.9% and 16.9% respectively, p 0.03) were found more often in diseased animals. BPI3V was found in a few early outbreaks, which might suggest involvement in early outbreaks. It appears to be difficult to associate specific pathogens to outbreaks at the species level. BRD is the major reason for treatment with antimicrobials. More specific knowledge about the association between pathogens and health/disease could help to reduce antimicrobial use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID-19) remain partially described. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID-19 patients with OD (OD group) and patients without OD (no-OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no-OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no-OD group (odds ratio [OR] = 0.536 [0.293-0.981], p = 0.041 and OR = 0.222 [0.056-0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no-OD group (OR = 0.170 [0.064-0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474-42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246-15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746-4.167], p < 0.001) and facial pain (OR = 2.901 [1.441-5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no-OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID-19 possibly due to methodological bias., (© 2022 Wiley Periodicals LLC.)

Objectives: Breathlessness is common among terminally ill patients with cardiorespiratory disease or cancer. The experience may induce secondary physiological and behavioral responses that limit patient well-being and independence and cause emotional distress., Methods: We conducted a meta-analysis on randomized controlled trials (RCTs) that examined the effectiveness of fan blowing on breathlessness among patients with cardiorespiratory diseases or cancer. The PubMed, Cochrane Library, Embase, SCOPUS, and CINAHL databases were searched to retrieve potential articles. The primary outcome was breathlessness severity. The secondary outcomes were SpO 2 , anxiety, depression, and quality of life. Also, we presented the changes of vital signs and subjective feeling of a male patient who used fan blowing for relieving his breathlessness., Results: Eight RCTs were available for analysis. The pooled results demonstrated no significant difference in breathlessness severity between fan-to-face blowing and control methods (standard mean difference: -0.21, 95% confidence interval: -.59 to .17); however, a significant reduction in breathlessness severity was observed in the short-time intervention compared with long-time intervention. A trend occurred toward significance in the reduction of respiratory rate in fan-to-face blowing compared with control methods (MD: -.64, 95% CI: -1.37 to .09). No differences were observed between groups in oxygen saturation, anxiety, depression, or QoL. The male patient who used fan blowing showed an improved vital signs and a satisfied subjective feeling., Conclusions: Consistent short-time fan-to-face blowing is effective for relieving breathlessness among conscious terminally ill patients with cardiorespiratory diseases or cancer. The use of this convenient method for relieving breathlessness symptoms in terminally ill patients is recommended.

This study aimed to investigate the prevalence at both farm-level and calf-level and to identify the risk factors of respiratory bacterial pathogens in dairy calves in Taiwan. The status of bovine respiratory disease (BRD) was evaluated by using the Wisconsin scoring system from a total of 400 pre-weaned calves from 32 different farms in Taiwan, then the nasopharyngeal swabs were collected. The prevalence of respiratory pathogens was 84.37% at farm-level and 45.50% at calf-level, and Pasteurella multocida (P. multocida) was the most prevalent pathogen. The presence of Mycoplasma bovis (M. bovis), P. multocida, Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni) were all higher in BRD positive calves than BRD negative calves, but only in H. somni was significant (P<0.001). Then nine farm management risk factors were analyzed by using multivariate logistic regression models to determine the risk factors of respiratory bacterial pathogens (farm and calf-level). In the result at farm-level, only unheated colostrum was significantly associated with pathogen positive farms (Odds Ratio (OR)=11.43). At calf-level, the predominant risk factor for each pathogen, M. bovis, P. multocida, M. haemolytica and H. somni, was late first colostrum feeding (OR=272.82), unheated colostrum (OR=3.41), waste milk feeding (OR=6.59) and high pneumonia treatment cost (OR=2.52), respectively. For effective preventive measures, farmer education on milk and colostrum feeding are urgently warranted.

BACKGROUND The aim of this study was to explore the relationship between C-reactive protein (CRP) and respiratory diseases in patients with diabetic retinopathy. MATERIAL AND METHODS We identified 855 patients with diabetic retinopathy who met the inclusion criteria from the "Diabetes Complications Data Set" in the National Population Health Data Center. We divided patients into 3 groups according to CRP tertiles: Q1 (<0.3 mg/dL), Q2 (0.3-0.35 mg/dL), and Q3 (>0.35 mg/dL). A multivariate logistic regression model was used to evaluate the relationship between CRP and respiratory diseases. The area under the receiver operating characteristic (ROC) curve was used to investigate the independent predictive effect of CRP on respiratory diseases. RESULTS Of the 855 patients with diabetic retinopathy, 137 (16%) had respiratory diseases. Prevalence of respiratory diseases gradually increased with an increase in CRP level (P for trend=0.001). With CRP as a continuous variable in the logistic regression model adjusted for confounding factors (model 3), the odds ratio (OR) per 1 standard deviation increment of CRP was 1.25 (95% CI 1.07-1.45, P=0.004). When the lowest CRP tertile group was used as the reference group, the OR of the highest CRP tertile group was 1.99 (95% CI 1.22-1.3.26, P=0.006). Adding CRP to the risk factor model increased the area under the ROC curve (0.68 vs 0.65, P=0.017). Subgroup analysis showed that the relationship between CRP and respiratory diseases had no potential heterogeneity among subgroups. CONCLUSIONS CRP can be used as an effective biomarker in predicting risk of respiratory diseases in patients with diabetic retinopathy.

Background: There are limited data to detail the perioperative anesthetic management and the incidence of postoperative respiratory complications among patients requiring an anesthetic procedure while being SARS-CoV-2 positive or suspected., Methods: An observational multicenter cohort study was performed including consecutive patients who were SARS-CoV-2 confirmed or suspected and who underwent scheduled and emergency anesthesia between March 17 and May 26, 2020., Results: A total of 187 patients underwent anesthesia with SARS-CoV-2 confirmed or suspected, with ultimately 135 (72.2%) patients positive and 52 (27.8%) negative. The median SOFA score was 2 [0; 5], and the median ARISCAT score was 49 [36; 67]. The major respiratory complications rate was 48.7% (n = 91) with 40.4% (n = 21) and 51.9% (n = 70) in the SARS-CoV-2-negative and -positive groups, respectively (p = 0.21). Among both positive and negative groups, patients with a high ARISCAT risk score (> 44) had a higher risk of presenting major respiratory complications (p < 0.01 and p = 0.1, respectively)., Discussion: When comparing SARS-COV-2-positive and -negative patients, no significant difference was found regarding the rate of postoperative complications, while baseline characteristics strongly impact these outcomes. This finding suggests that patients should be scheduled for anesthetic procedures based on their overall risk of postoperative complication, and not just based on their SARS-CoV-2 status., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) affects all components of the respiratory system, including the neuromuscular breathing apparatus, conducting and respiratory airways, pulmonary vascular endothelium, and pulmonary blood flow. In contrast to other respiratory viruses, children have less severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A minority of children experience a post-infectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. The reason for the lower burden of symptomatic disease in children is not yet clear, but several pathophysiological characteristics are postulated. The SARS-CoV-2 pandemic has brought distinct challenges to the care of children globally. Proper recommendations have been proposed for a range of non-asthmatic respiratory disorders in children, including primary ciliary dyskinesia and cystic fibrosis. These recommendations involve the continuation of the treatment during this period and ways to maintain stability. School closures, loss of follow-up visit attendance, and loss of other protective systems for children are the indirect outcomes of measures to mitigate the COVID-19 pandemic. Moreover, COVID-19 has reshaped the delivery of respiratory care in children, with non-urgent and elective procedures being postponed, and distancing imperatives have led to rapid scaling of telemedicine. The pandemic has seen an unprecedented reorientation in clinical trial research towards COVID-19 and a disruption in other trials worldwide, which will have long-lasting effects on medical science. In this narrative review, we sought to outline the most recent findings on the direct and indirect effects of SARS-CoV-2 pandemic on pediatric respiratory chronic diseases other than asthma, by critically revising the most recent literature on the subject., (© 2021. The Author(s).)

Background: Children with complex chronic multisystemic diseases frequently require care from multiple pediatric subspecialists. The aerodigestive program is a multidisciplinary program that diagnoses and treats pediatric patients with complex multi-systematic problems affecting airway, breathing, feeding, swallowing, or growth. The aim of this study is to present the protocol of the aerodigestive program of a children's hospital., Methods and Design: This study is a prospective study to evaluate and compare the overall improvement of patients' objective and subjective conditions before and after the AeroDigestive Team (ADT) program. Among children from 1 month to 18 years of age, patients with complex problems of the airway, breathing, feeding, swallowing, or growth meeting at least two parameters of the inclusion criteria were enrolled. The overall process included referral based on the inclusion criteria, enrollment of ADT program with informed consents, interview and questionnaire for assessing patients' medical condition, prescheduling appointment, multi-specialists' evaluation, monthly team meetings, wrap-up discussion with the patients and family, therapeutic intervention, and follow-up at 6 months with the assessment of outcome measures. The outcome was evaluated objectively and subjectively. The objective outcome measure was divided into surgical or medical intervention, assessment of changes in medical condition, and follow-up study. Both caregiver interviews and questionnaires using a scoring system were used as subjective outcome measures before and after the ADT program. Children were scheduled to be followed-up at 6 months after the interventions or ADT meeting., Discussion: The aerodigestive program is expected to provide comprehensive and multidisciplinary management of children with complex airway and digestive tract disorders., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology., Design and Setting: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort., Patients: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113)., Results: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values., Conclusion: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To identify in the scientific literature the clinical overview of the pediatric population that tested positive for SARS-CoV-2 and care recommendations and recommendations among children who tested positive for SARS-CoV-2 in the scientific literature., Method: Rapid review based on the guidelines of the Joana Briggs Institute: elaboration of the research question, structured search of the literature in April 2020, in nine databases, selection and critical analysis of the eighteen primary studies (using two instruments to assess methodological quality), elaboration of the synthesis, incorporation of suggestions and dissemination., Result: The most frequent clinical overview was respiratory, gastrointestinal symptoms and fever. The images showed irregular frosted glass opacification. It is recommended to screen the pediatric population and family members who show signs and symptoms and to adopt isolation for more than fourteen days., Conclusion: The clinical overview in pediatric population is varied, not exclusively with respiratory symptoms, and a significant number of asymptomatic patients. The importance of new investigations is highlighted, such as randomized clinical trial or cohort studies, identifying their participation in the transmission of COVID-19.

Background: Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem., Methods: Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution., Results: SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS., Conclusions: COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Down syndrome (DS) is the most common chromosomal condition. Anatomical and functional variations in the upper and lower airways are component manifestations of the syndrome and increase the risk of various medical problems. The objective of this study was to determine the prevalence of otorhinolaryngological and respiratory diseases in a DS outpatient clinic over a 3-year period. Medical records data from 1207 patients were retrospectively reviewed. Newborn Hearing Screening was positive in 7.1% of patients. Brainstem auditory evoked potential was performed in 1101 children and showed a hearing loss of 19.8% in the first year. It was positive in 21% of 1021 exams. Audiometry was altered in 64 of 994 exams (6.4%), showing a conductive loss in 90%. Adenotonsillectomy was performed in 308 (25.5%) patients, and 169 (14.0%) required serous otitis ventilation tubes. Asthma was observed in 140 (11.6%) patients, and allergic rhinitis in 544 (56.6%). There were hospitalizations for invasive infection in 480 (39.8%) children, and two (0.2%) patients had severe septicemia from pulmonary focus. Five (0.4%) infants had laryngotracheomalacia, and one patient had anomalous right tracheal bronchus. Recognizing the prevalence of respiratory and otorhinolaryngological disorders in patients with DS allows the promotion of optimal follow-up and early treatment, preventing the development of sequelae., (© 2021 Wiley Periodicals LLC.)

Sustainable livestock production requires links between farm characteristics, animal performance and animal health to be recognised and understood. In the pig industry, respiratory disease is prevalent, and has negative health, welfare and economic consequences. We used national-level carcass inspection data from the Food Standards Agency to identify associations between pig respiratory disease, farm characteristics (housing type and number of source farms), and pig performance (mortality, average daily weight gain, back fat and carcass weight) from 49 all in/all out grow-to-finish farms. We took a confirmatory approach by pre-registering our hypotheses and used Bayesian multi-level modelling to quantify the uncertainty in our estimates. The study findings showed that acquiring growing pigs from multiple sources was associated with higher respiratory condition prevalence. Higher prevalence of respiratory conditions was linked with higher mortality, and lower average daily weight gain, back fat and pig carcass weight. Our results support previous literature using a range of data sources. In conclusion, we find that meat inspection data are more valuable at a finer resolution than has been previously indicated and could be a useful tool in monitoring batch-level pig health in the future.

Abstract: The experience and causes of pain in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) have not been clarified.This study aimed to determine the prevalence and severity of bodily pain (BP) in patients with NTM-PD. We also investigated the clinical indicators that contribute to pain.We used a retrospective cross-sectional study design. The participants were 114 NTM-PD patients (109 women) with a mean age of 65 years. The prevalence and severity of pain were measured using 2 items from the 36-Item Short Form Survey version 2 (SF-36), and the BP score was calculated. Functional limitation due to dyspnea was quantified using the Modified Medical Research Council Dyspnea Scale (mMRC), depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); health-related quality of life was assessed using the Leicester Cough Questionnaire (LCQ), and exercise tolerance was measured using the Incremental Shuttle Walk Test (ISWT).Pain was reported by 70.2% of the patients (n = 80), and of these, 35.7% (n = 25) reported moderate to very severe pain. NTM-PD patients with high levels of pain had significantly higher scores on the mMRC, CES-D, and PSQI scores, and significantly lower performance on the ISWT and LCQ. Multiple regression analysis identified ISWT, CES-D, and PSQI as independent factors that affected BP scores.Our findings suggest that pain significantly impacts daily life associated with reduced exercise tolerance, the presence of depressive symptoms, and poor sleep quality in patients with NTM-PD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough., Competing Interests: Conflict of Interest Dr. Hiroshi Mukae received honoraria from Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., KYOLIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Taisho Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., and AstraZeneca K.K., a research grant from Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Taisho Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., KYORIN Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd.; Dr. Takeshi Kaneko received honoraria from Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., and Meiji Seika Pharma Co., Ltd., and a research grant from Teijin Home Healthcare Ltd., Ono Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd.; Dr. Toshio Katsunuma received honoraria from KYORIN Pharmaceutical Co., Ltd., Maruho Co., Ltd. and Torii Pharmaceutical Co., Ltd.; Dr. Akio Niimi received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., MSD K.K., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K. and Novartis Pharma K.K., a research grant from Novartis Pharma K.K., Boston Scientific Corporation, MSD K.K., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., KYORIN Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd.; Dr. Hiroto Matsuse received honoraria from MSD K.K., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., and Astellas Pharma Inc.; Dr. Kazuhiro Yatera received honoraria from AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer lngelheim Co., Ltd., Astellas Pharma Inc., GlaxoSmithKline K.K., and KYORIN Pharmaceutical Co., Ltd., and subsidies or donations from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Shionogi & Co., Ltd., Teijin Home Healthcare Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Novartis Pharma K.K., and Nippon Boehringer Ingelheim Co., Ltd.; Dr. Arata Azuma received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Dr. Hirokazu Arakawa received subsidies or donations from Novartis Pharma K.K.; Dr. Takashi Iwanaga received honoraria from KYORIN Pharmaceutical Co., Ltd., a research grant from KYORIN Pharmaceutical Co., Ltd., Pearl Therapeutics, Inc., and Meiji Seika Pharma Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., Teijin Pharma Ltd., and KYORIN Pharmaceutical Co., Ltd.; Dr. Yasuhiro Gon received honoraria from Novartis Pharma K.K., AstraZeneca K.K., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd., and KYORIN Pharmaceutical Co., Ltd., and a research grant from Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Hirokazu Sakamoto received a research grant from Sanofi K.K. and Novartis Pharma K.K.; Dr. Yoko Shibata received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and GlaxoSmithKlein K.K.; Dr. Tsutomu Tamada serves as a consultant to Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Yasuhiko Nishioka received honoraria from Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and MSD K.K., a research grant from Taiho Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Bonac Corporation, and subsidies or donations from Ono Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Asahi Kasei Pharma Corporation, and Chugai Pharmaceutical Co., Ltd.; Dr. Shigeharu Fujieda received patent royalties and/or licensing fees from KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Taiho Pharmaceutical Co., Ltd., and a research grant from Mitsubishi Tanabe Pharma Corporation, Tsumura Co., Ltd., Maruho Co., Ltd., and Sanofi K.K.; Dr. Naoyuki Miyashita received honoraria from Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Astellas Pharma Inc., Pfizer Japan Inc., and Taisho Toyama Pharmaceutical Co., Ltd.; Dr. Akihito Yokoyama received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., GlaxoSmithKlein K.K., and Sanofi K.K., and a research grant from Astellas Pharma Inc. and Ono Pharmaceutical Co., Ltd. Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest.Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Sarcopenia and frailty are strongly associated with disease incidence and mortality. However, there is limited evidence regarding their joint association with health outcomes. This study aimed to investigate the joint association of sarcopenia and frailty with cardiovascular disease (CVD), respiratory disease and cancer incidence and mortality as well as all-cause mortality in middle-aged and older adults in the UK Biobank study., Methods: 316,980 UK Biobank participants were included in this prospective study (53.1% women). Sarcopenia was defined according to the EWGSOP2 2019. Frailty was defined using a modified version of the Fried criteria. Combined classifications of sarcopenia and frailty were generated with the following seven subgroups derived: i) normal, ii) non-sarcopenic/pre-frail, iii) non-sarcopenic/frail, iv) pre-sarcopenic/pre-frail, v) pre-sarcopenic/frail, vi) sarcopenic/pre-frail, and vii) sarcopenic/frail. No participants had (pre)sarcopenia but not frailty. Associations between these exposures and health outcomes (incidence and mortality from cardiovascular and respiratory diseases, cancer, as well as, all-cause mortality) were investigated using Cox-proportional hazard models., Results: 51.7% of the participants were not sarcopenic nor frail (normal), 41.3% were pre-frail or frail, 6.5% pre-sarcopenia and frail (including pre-frail) and 0.5% as having both sarcopenia and frailty (including pre-frailty). The combination sarcopenic/frail showed the strongest association with CVD (HR: 1.68 [95% CI: 1.22 to 2.30]) and respiratory disease incidence (HR: 1.77 [95% CI: 1.40 to 2.24]) and for mortality from all-cause (HR: 2.27 [95% CI: 1.64 to 3.13]), respiratory disease (HR: 3.50 [95% CI: 1.97 to 6.23]), and cancer (HR: 1.92 [95% CI: 1.08 to 3.38]). Finally, when we investigated the associations between the outcomes and exposures by age groups (≥and <60 years), we identified that, for many outcomes and categories, the associations were higher in younger individuals compared with older adults., Conclusion: Our findings indicate that different combinations of sarcopenia and frailty were associated with adverse health outcomes, highlighting the joint association between both conditions. However, those individuals with sarcopenia and frailty showed the strongest associations with CVD and respiratory disease incidence and mortality for all-cause and respiratory disease and cancer., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To determine if administration of oral prednisolone to preschool children with acute wheeze alters respiratory outcomes., Design: Double-blind, randomised, placebo-controlled equivalence trial., Setting: Three hospitals in New Zealand., Patients: 477 children aged 24-59 months with acute wheeze associated with respiratory illness., Interventions: 2 mg/kg (maximum 40 mg) oral prednisolone or similar placebo, once daily for 3 days., Main Outcome Measures: Primary outcome was change in Preschool Respiratory Assessment Measure (PRAM) score 24 hours after intervention. Secondary outcomes included PRAM score at 4 hours, length of emergency department and inpatient stays, admission and representation rates, time to return to normal activities and use of additional oral prednisolone or intravenous medications. Analysis was by intention-to-treat., Results: There was no difference between groups for change in PRAM score at 24 hours (difference between means -0.39, 95% CI -0.84 to 0.06, p=0.09). Absolute PRAM score was lower in the prednisolone group at 4 hours (median (IQR) 1 (0-2) vs 2 (0-3), p=0.01) and 24 hours (0 (0-1) vs 0 (0-1), p=0.01), when symptoms had resolved for most children regardless of initial treatment. Admission rate, requirement for additional oral prednisolone and use of intravenous medication were lower in the prednisolone group, although there were no differences between groups for time taken to return to normal activities or rates of representation within 7 days., Conclusion: Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objective: The course of COVID-19 caused by the SARS-CoV-2 may be aggravated by bioaerosols containing other viruses, bacteria, and fungi, occurring mainly in the occupational environment. Hence, the diagnostics and treatment of COVID-19 should address such a possibility in the anamnesis, treatment and final recommendations for avoiding of adverse exposure., Abbreviated Description of the State of Knowledge: As SARS-CoV-2 attacks primarily the respiratory system and the severe manifestation of COVID-19 is interstitial pneumonia, diagnostics should include the following clinical and laboratory examinations: chest X-ray; high resolution computed tomography (HRCT); pulmonary function tests; arterial-blood gas test; genetic tests for the presence of SARS-CoV-2, in the future with the use of highly specific and sensitive nano-based biosensors; tests for the presence of specific immunity against the antigens of microorganisms causing other infectious or allergic pulmonary diseases (in the case of anamnestic indications). Because an universally accepted treatment for COVID-19 does not exist, the hitherto prescribed antiviral and immune-modulating drugs should be used be with caution. In many cases, a better alternative could be a safe supportive therapy, such as supplementation of the diet with probiotics, prebiotics, vitamins and microelements., Summary: The most important preventive measures against COVID-19 should include: vaccination; the use of filter or surgical masks; disinfection and sterilization; maintaining of well-functioning ventilation and air conditioning systems; reduction of the community air pollution which has been identified as an important factor increasing the COVID-19 severity. In the choice of preventive measures, the above should be considered for their potential efficacy against other bioaerosols as potential disease-aggravating agents.

Unintentional weight loss is a common clinical problem with a broad differential diagnosis that is clinically important because of the associated risks of morbidity and mortality. Community-dwelling adults are often diagnosed with malignancy, nonmalignant gastrointestinal disorders, and psychiatric disorders as the cause of unintentional weight loss, whereas institutionalized older adults are diagnosed most often with psychiatric disorders. Up to a quarter of patients do not have a diagnosis after comprehensive workup, and close follow-up is warranted. Treatment involves management of underlying causes., Competing Interests: Disclosure Dr. Shaw supported in part by a Joachim Silbermann Family Clinical Scholar Award in Geriatrics from the Rosanne H. Silbermann Foundation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The efficacy of neuraminidase inhibitors on improvement of respiratory symptoms triggered by influenza in patients with pre-existing chronic respiratory diseases is unknown., Methods: This 2-week, randomized, open-label study evaluated intravenous peramivir 600 mg on two consecutive days (peramivir-repeat), peramivir 300 mg single dose (peramivir-single), and oral oseltamivir 75 mg twice daily for 5 days in patients with confirmed influenza and chronic respiratory diseases. Patients recorded symptom scores daily. The primary endpoint of cumulative area of time vs symptoms (CATVS) was expressed as an index value of area under the curve vs time of the total score of cough, sore throat, and nasal congestion from baseline to 2 weeks., Results: Of 214 randomized patients, 209 (56% female, 77% aged <65 years, 94% outpatients, 91% bronchial asthma, 62% influenza A) received ≥1 dose of study drug. Mean (standard deviation) CATVS was similar for peramivir-repeat (782.78 [487.17]) vs peramivir-single (717.35 [347.55]; P = .4371), and for peramivir-repeat vs oseltamivir (856.34 [404.99]; P = 1.00). However, CATVS was significantly shorter for peramivir-single vs oseltamivir, with an estimated treatment difference (TD) of -145.07 (95% confidence interval: -284.57, -5.56; P = .0416). In subgroup analyses, CATVS was significantly shorter for peramivir-single vs oseltamivir among patients with influenza A (TD: -206.31 [-383.86, -28.76]; P = .0231), bronchial asthma (TD: -156.57 [-300.22, -12.92]; P = .0328), baseline respiratory severity score <5 (TD: -265.32 [-470.42, -60.21]; P = .0120), and age <65 (TD: -184.30 [-345.08, -23.52]; P = .0249)., Conclusions: In patients with chronic respiratory diseases, peramivir-single was not significantly different from peramivir-repeat and was more effective than oseltamivir at alleviating respiratory symptoms., (© 2020 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

The COVID-19 pandemic causes severe morbidity and mortality. This multi-country study aimed to explore risk factors that drive mortality in COVID-19 patients who received neither dexamethasone nor remdesivir. We analyzed a cohort of 568 survivors and 507 non-survivors from China, European regions, and North America. Elderly males ≥70 years accounted for only 25% of survivors, but this rate was significantly higher in non-survivors from China (55%), European regions (63%), and North America (47%). Compared with survivors, non-survivors had more incidences of comorbidities such as cerebrovascular disease and chronic obstructive pulmonary disease (COPD, p-values<0.05). Survival analyses revealed age, male gender, shortness of breath, cerebrovascular disease, and COPD as mortality-associated factors. Survival time from symptom onset was significantly shorter in elderly versus young patients (median: 29 versus 62 days), males versus females (median: 46 versus 59 days), and patients with versus without comorbidities (mean: 41 versus 61 days). Mortality risk was higher in elderly males with comorbidities than in young females without comorbidities (p-value<0.01). Elderly male survivors with comorbidities also had longer hospital stays than other survivors (25 versus 18.5 days, p-value<0.01). Overall, the high mortality risk in elderly males with COVID-19-associated comorbidities supports early prevention and critical care for elderly populations.

Background/aim: Dyspnea is the subjective feeling of breathing discomfort, which is a significant problem for patients with heart and respiratory disease and also an important determinant of exercise tolerance, quality of life, and mortality in various diseases. Most of the scales are not enough to investigate the multidimensional effects of dyspnea; therefore, the Multidimensional Dyspnea Profile (MDP) was developed and validated in many languages. This study aimed to translate and culturally adapt the MDP into Turkish and investigate the psychometric properties of this adapted version in outpatients with respiratory disease., Materials and Methods: The MDP was translated and culturally adapted into Turkish following published guidelines. A total of 170 outpatients with respiratory disease were included to assess psychometric properties. The factorial structure was investigated using a principal component analysis. Two situations were used in this study evaluating dyspnea in activity-related and resting conditions. We formulated 17 hypotheses for each MDP domain (in total 68) to assess construct validity, and correlations were investigated between the MDP and measures of body mass index, pulmonary function test, other dyspnea assessments, anxiety, depression, and health-related quality of life. To investigate the test-retest reliability, the MDP was administered again after 1-h and 1 week, Results: Internal consistency of the MDP was excellent (Cronbach’s alpha coefficients ranged from 0.89 to 0.93). The exploratory factor analysis revealed 2 components explaining a 70% and 76% variance. Overall, 64 of the 68 predetermined hypotheses (94%) were confirmed to test construct validity. The MDP showed excellent test-retest reliability for a 1-hperiod (intraclass correlation coefficient values ranged from 0.98 to 0.99). However, test-retest reliability decreased moderate-to-high after 1 week (0.53–0.80)., Conclusion: The MDP was successfully translated and culturally adapted into Turkish and this version showed good psychometric properties including the factorial structure, internal consistency, test-retest reliability, and construct validity to assess multidimensional aspects of dyspnea., Competing Interests: All authors report no conflict of interest that may have influenced either the conduct or the presentation of the research., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objectives: The aim of this study was to evaluate the results of serum allergen-specific IgE testing in cats with a clinical diagnosis of asthma and to determine if the number of allergens with positive IgE reactivity and magnitude of positive IgE responses would be associated with the severity of clinical signs or airway eosinophilia., Methods: Medical records from 2008 to 2018 were retrospectively reviewed. Inclusion required a diagnosis of feline asthma based on consistent clinicopathologic features and bronchoalveolar lavage (BAL) cytology with >10% eosinophils; additionally, cats needed to have the results of serum allergen-specific IgE tests., Results: Eighteen cases satisfied the inclusion criteria. Median age was 5 years and the most common presenting clinical sign was cough (n = 10/18). Most cats lived exclusively indoors (n = 13/18). The median percentage of BAL eosinophils was 47%. Serum allergen-specific IgE testing supported an underlying allergic etiology in 14/18 (78%) cats, with all but one having polysensitization. The severity of clinical signs and magnitude of airway eosinophilia did not correlate with the degree of positive IgE reactivity., Conclusions and Relevance: This study identified a strong association between the identification of allergen-specific IgE and cats with asthma, and the majority of these cats were polysensitized. However, larger numbers of allergens with positive IgE reactivity or magnitude of IgE reactivity were not significantly associated with clinical severity or airway eosinophilia. Knowledge of positive allergen-specific IgE results could guide allergen avoidance, regardless of the magnitude of IgE reactivity.

Background: Sarcopenic obesity is defined as a combination of sarcopenia and obesity. Previous studies have shown a positive association between sarcopenia and respiratory disease, while other studies have identified that obese individuals have a lower risk for respiratory diseases. This study aimed to investigate the association of obesity, sarcopenia and sarcopenic obesity with respiratory disease incidence and mortality., Methods: Data from 170,083 participants from the prospective UK Biobank study were included. Sarcopenic obesity was defined as the combination of sarcopenia with one of the following obesity criteria: BMI ≥30 kg/m 2 , waist circumference (WC) ≥ 88 cm in women or ≥ 102 cm in men, or the two highest sex-specific quintiles of body fat. Respiratory disease incidence and mortality were the outcomes., Results: The mean follow-up period was 7.0 years. 5459 (3.2%) participants developed respiratory diseases and 780 (0.5%) died from respiratory diseases. Compared to individuals without obesity or sarcopenia, those who were obese (Hazard Ratio (HR): 1.13 [95 CI: 1.03; 1.23]), sarcopenic (HR: 1.23 [95% CI: 1.10; 1.36]) or sarcopenic obese (based on BMI) (HR: 1.51 [95% CI: 1.30; 1.77]), had a higher risk of respiratory disease incidence. However, the risk of respiratory disease mortality was higher in sarcopenic individuals and lower in obese individuals. No associations were identified between sarcopenic obesity and respiratory mortality (HR: 1.12 [95% CI: 0.76; 1.63]). Similar patterns were found when obesity was defined using WC or body fat., Conclusion: Obesity, sarcopenia and sarcopenic obesity were associated with a higher risk of respiratory disease incidence. However, while obesity was associated with lower, and sarcopenia with higher respiratory mortality risk, no associations between sarcopenic obesity and respiratory mortality were identified., Competing Interests: Conflict of Interest None to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Chest pain is a common presenting complaint in the primary care setting. Imaging plays a key role in the evaluation of the multiple organ systems that can be responsible for chest pain. With numerous imaging modalities available, determination of the most appropriate test and interpretation of the findings can be a challenge for the clinician. In this 2-part series, we offer resources to guide primary care physicians in the selection of imaging studies and present the imaging findings of various causes of nonemergent chest pain. In Part 2, we focus on the radiologic appearance of common noncardiac sources of chest pain, including gastrointestinal, pulmonary, and musculoskeletal etiologies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To investigate the risk of mortality associated with exposure to codeine, considering various risk groups, using population-based national insurance claims data.National sample cohort data from the National Health Insurance Service of South Korea (2002-2013) was used in this case-control study. Cases were defined as patients with a death record between January 1, 2002 and December 31, 2013. Each case was matched to 10 controls based on age, sex, baseline comorbidities, and year of death. Definition of exposure was codeine prescription in 30 days prior to death and sensitivity analyses were performed for 15 and 60-day exposures. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusting for benzodiazepine, other opioids, anesthetics, hypnotics, CYP2D6 inducer, CYP3A4 inducer, and the Charlson comorbidity index.A total of 19,341 cases and 185,700 matched controls were included. The overall risk associated with codeine use and mortality risk was not significant (aOR 1.08, 95% CI 1.00-1.16). Sensitivity analyses with different exposure time window also presented similar insignificant results. However, in the subgroup analyses, codeine use was associated with an increased risk of mortality in the >85-year-old age group (aOR 2.38, 95% CI 1.26-4.48) and patients with respiratory disease (aOR 1.29, 95% CI 1.17-1.42).Although no statistically significant association was found in codeine exposure and mortality risk between cases and controls, we demonstrated that the elderly over 85 years old and patients with respiratory disease are associated with a higher risk with codeine exposure. Therefore, a more cautious practice of codeine prescription in these groups might be needed.

The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D 3 supplementation might help to reduce respiratory disease mortality. We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30-50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50-75 years from Saarland, Germany. Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D 3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.