Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease.

OBJECTIVE: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease. METHODS: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities. RESULTS: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect. CONCLUSIONS: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

Face mask use during the COVID-19 pandemic was associated with breathing difficulties in adolescent patients with asthma.

AIM: Face masks have been used to prevent severe acute respiratory syndrome coronavirus-2 transmission. We investigated the impact of face mask use on paediatric patients with asthma. METHODS: Between February 2021 and January 2022, we surveyed adolescents aged 10-17 attending the paediatric outpatient clinic at the Lillebaelt Hospital, Kolding, Denmark with asthma, other breathing problems or no breathing problems. RESULTS: We recruited 408 participants (53.4% girls) with a median age of 14 years: 312 in the asthma group, 37 in the other breathing problems group and 59 in the no breathing problems group. Most participants experienced mask-related breathing impairment. The relative risk (RR) of experiencing severe breathing problems, compared to no problems, was more than four times as high for adolescents with asthma (RR 4.6, 95% CI 1.3-16.8, p = 0.02) than adolescents with no breathing problems. More than a third (35.9%) of the asthma group experienced mild asthma and 3.9% had severe asthma. Girls experienced more mild (RR 1.9, 95% CI 1.2-3.1, p < 0.01) and severe (RR 6.6, 95% CI 3.1-13.8, p < 0.01) symptoms than boys. Age had no effect. Adequate asthma control minimised negative effects. CONCLUSION: Face masks caused significant breathing impairment in most adolescents, particularly in those with asthma.

From Microscopic Droplets to Macroscopic Crowds: Crossing the Scales in Models of Short-Range Respiratory Disease Transmission, with Application to COVID-19.

Short-range exposure to airborne virus-laden respiratory droplets is an effective transmission route of respiratory diseases, as exemplified by Coronavirus Disease 2019 (COVID-19). In order to assess the risks associated with this pathway in daily-life settings involving tens to hundreds of individuals, the chasm needs to be bridged between fluid dynamical simulations and population-scale epidemiological models. This is achieved by simulating droplet trajectories at the microscale in numerous ambient flows, coarse-graining their results into spatio-temporal maps of viral concentration around the emitter, and coupling these maps to field-data about pedestrian crowds in different scenarios (streets, train stations, markets, queues, and street cafés). At the individual scale, the results highlight the paramount importance of the velocity of the ambient air flow relative to the emitter's motion. This aerodynamic effect, which disperses infectious aerosols, prevails over all other environmental variables. At the crowd's scale, the method yields a ranking of the scenarios by the risks of new infections, dominated by the street cafés and then the outdoor market. While the effect of light winds on the qualitative ranking is fairly marginal, even the most modest air flows dramatically lower the quantitative rates of new infections.

Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications.

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.

[Review of methodological approaches for the assessment of social and medical rehabilitation in the cardio-respiratory system diseases at the post-COVID period]. / Obzor metodologicheskikh podkhodov otsenki sotsial'no-meditsinskoi reabilitatsii pri zabolevaniyakh kardiorespiratornoi sistemy v postkovidnyi period.

There is currently no systematic relationship between the quantification of funding for the treatment and rehabilitation of cardio-respiratory diseases and the length of a citizen's working life. The development of a universal evaluation methodology that can be used for qualitative and quantitative evaluation of the effectiveness of social and medical rehabilitation is a relevant area of research. The survey contains an analysis of the scientific approaches used in research on social and medical rehabilitation, as well as the development of medical and social rehabilitation and health resort and spa treatment, and to assess the impact of medical rehabilitation on restoration of ability to work. On the basis of the data obtained, a set of indicators for the assessment of the socio-medical rehabilitation of diseases of the cardio-respiratory system at the post-COVID period is proposed, which in the future will serve as a methodological tool in the field of medical and social rehabilitation, health resort and spa activities and at all stages of rehabilitation and preventive medicine.

The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside.

The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.

Changes in all-cause and cause-specific excess mortality before and after the Omicron outbreak of COVID-19 in Hong Kong.

Background: While coronavirus 2019 (COVID-19) deaths were generally underestimated in many countries, Hong Kong may show a different trend of excess mortality due to stringent measures, especially for deaths related to respiratory diseases. Nevertheless, the Omicron outbreak in Hong Kong evolved into a territory-wide transmission, similar to other settings such as Singapore, South Korea, and recently, mainland China. We hypothesized that the excess mortality would differ substantially before and after the Omicron outbreak. Methods: We conducted a time-series analysis of daily deaths stratified by age, reported causes, and epidemic wave. We determined the excess mortality from the difference between observed and expected mortality from 23 January 2020 to 1 June 2022 by fitting mortality data from 2013 to 2019. Results: During the early phase of the pandemic, the estimated excess mortality was -19.92 (95% confidence interval (CI) = -29.09, -10.75) and -115.57 (95% CI = -161.34, -69.79) per 100 000 population overall and for the elderly, respectively. However, the overall excess mortality rate was 234.08 (95% CI = 224.66, 243.50) per 100 000 population overall and as high as 928.09 (95% CI = 885.14, 971.04) per 100 000 population for the elderly during the Omicron epidemic. We generally observed negative excess mortality rates of non-COVID-19 respiratory diseases before and after the Omicron outbreak. In contrast, increases in excess mortality were generally reported in non-respiratory diseases after the Omicron outbreak. Conclusions: Our results highlighted the averted mortality before 2022 among the elderly and patients with non-COVID-19 respiratory diseases, due to indirect benefits from stringent non-pharmaceutical interventions. The high excess mortality during the Omicron epidemic demonstrated a significant impact from the surge of COVID-19 infections in a SARS-CoV-2 infection-naive population, particularly evident in the elderly group.

Effect of Nebulized BromAc on Rheology of Artificial Sputum: Relevance to Muco-Obstructive Respiratory Diseases.

Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions.

Association of ovine gammaherpesvirus 2 with an outbreak of acute respiratory disease in dairy cattle.

This study investigated the cause of an outbreak of an acute respiratory disease syndrome followed by episodes of diarrhea in a dairy cattle herd from Southern Brazil. Deep nasal swabs (DNS) from asymptomatic calves, calves with pulmonary discomfort, and diarrheic calves after episodes of respiratory distress were used in molecular assays designed to detect the principal pathogens associated with bovine respiratory disease (BRD). Fecal samples were used for the molecular detection of bovine enteric disease agents. Pulmonary tissues from three calves and a cow that died were evaluated by molecular assays to identify 11 agents associated with the development of BRD. The intestinal and pulmonary fragments of one calf and the cow revealed atrophic enteritis and interstitial pneumonia by histopathology, respectively. Immunohistochemistry (IHC) identified intralesional antigens of a malignant catarrhal fever virus, genus Macavirus, within epithelial cells of the lungs and intestines. Molecular assays amplified ovine gammaherpesvirus 2 (OvGHV2) from most of the DNS, and the pulmonary and intestinal fragments from the animals that died, confirming that the Macavirus identified by IHC was OvGHV2. Concomitant pulmonary infections of OvGHV2 with bovine gammaherpesvirus 6 and bovine coronavirus were identified. Additionally, bovine viral diarrhea virus 1b and Aichivirus B were detected in the fecal samples. These findings demonstrated that OvGHV2, a Macavirus, was the disease agent most frequently (81.2%; 13/16) associated with singular pulmonary infections during this outbreak of BRD, suggesting that this virus may be another potential agent of respiratory disease of cattle.

Impact of the COVID-19 pandemic on diagnosis of respiratory diseases in the Northern Metropolitan Area in Barcelona (Spain).

OBJECTIVE: The COVID-19 pandemic has had a great effect on the management of chronic diseases, by limiting the access to primary care and to diagnostic procedures, causing a decline in the incidence of most diseases. Our aim was to analyze the impact of the pandemic on primary care new diagnoses of respiratory diseases. METHODS: Observational retrospective study performed to describe the effect of COVID-19 pandemic on the incidence of respiratory diseases according to primary care codification. Incidence rate ratio between pre-pandemic and pandemic period was calculated. RESULTS: We found a decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications (J95). Instead, we found increases in flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). CONCLUSION: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic.

Effects of home healthcare for adults with chronic respiratory diseases and post-COVID-19 syndrome on hospital bed turnover rate: a protocol of systematic review with meta-analysis.

INTRODUCTION: Chronic respiratory diseases (CRDs) have a high prevalence, morbidity and mortality worldwide. After the COVID-19 pandemic, the number of patients readmitted after hospital discharge increased. For some populations, early hospital discharge and home healthcare may reduce health costs in patients treated at home when compared with those hospitalised. This study aims to systematically review the effectiveness of home healthcare for patients with CRDs and post-COVID-19 syndrome. METHODS AND ANALYSIS: We will search on MEDLINE, CENTRAL, Embase and PsycINFO. We will include randomised controlled trials (RCTs) and non-RCT studies reported in full text and abstracts. No language restriction will be applied. We will include studies related to adults with a diagnosis of CRDs or post-COVID-19 syndrome that compared in-patient hospital care with any home healthcare. We will exclude studies with participants with neurological, mental diseases, cancer or pregnant women. Two review authors will screen abstracts and select the eligible studies. To investigate the risk of bias, we will use the Cochrane 'Risk of Bias' tool for RCT, and the Risk of Bias In Non-randomised Studies-of Interventions for non-RCT. We will use the five Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) considerations to assess the quality of the evidence. Patients and the public will be involved in the preparation, execution and implementation phases of the review. ETHICS AND DISSEMINATION: No ethical approval is required because only published data will be analysed. The publication of the results in peer-reviewed journals and at relevant conferences will guide the direction of future research in the field and healthcare practice. The results will also be disseminated in plain language on social media to disseminate the knowledge to society and the public interested in the topic.

Post-COVID Interstitial Lung Disease-The Tip of the Iceberg.

The proportion of symptomatic patients with post-coronavirus 2019 (COVID-19) condition (long COVID) represents a significant burden on the individual as well as on the health care systems. A greater understanding of the natural evolution of symptoms over a longer period and the impacts of interventions will improve our understanding of the long-term impacts of the COVID-19 disease. This review will discuss the emerging evidence for the development of post-COVID interstitial lung disease focusing on the pathophysiological mechanisms, incidence, diagnosis, and impact of this potentially new and emerging respiratory disease.

Modeling of Respiratory Diseases Evolving with Fibrosis from Organoids Derived from Human Pluripotent Stem Cells.

Respiratory disease is one of the leading causes of morbidity and mortality worldwide. There is no cure for most diseases, which are treated symptomatically. Hence, new strategies are required to deepen the understanding of the disease and development of therapeutic strategies. The advent of stem cell and organoid technology has enabled the development of human pluripotent stem cell lines and adequate differentiation protocols for developing both airways and lung organoids in different formats. These novel human-pluripotent-stem-cell-derived organoids have enabled relatively accurate disease modeling. Idiopathic pulmonary fibrosis is a fatal and debilitating disease that exhibits prototypical fibrotic features that may be, to some extent, extrapolated to other conditions. Thus, respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or the one caused by SARS-CoV-2 may reflect some fibrotic aspects reminiscent of those present in idiopathic pulmonary fibrosis. Modeling of fibrosis of the airways and the lung is a real challenge due to the large number of epithelial cells involved and interaction with other cell types of mesenchymal origin. This review will focus on the status of respiratory disease modeling from human-pluripotent-stem-cell-derived organoids, which are being used to model several representative respiratory diseases, such as idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, and COVID-19.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

Pathophysiology of COVID-19 pneumonia and respiratory treatment.

COVID-19 pandemic has seen an unprecedented number of patients presenting with acute respiratory distress syndrome to the intensive care units all over the world. Between August and November 2022, we performed research on PubMed screening all publications on COVID-19 disease and respiratory failure and its treatment. In this review we focused on COVID-19 most common manifestations concerning lung function. The respiratory infection develops in three broad phases: early, intermediate, and late. The mainstay of the disease is the frequent presence of severe hypoxemia associated - at least at the beginning - to a near normal lung mechanics and PaCO2 tension. The management of symptomatic patients, progressing through these temporal phases, is not possible without understanding the pathophysiology underlying the respiratory manifestation.

The change in the relationship between temperature and respiratory diseases among children in Guangzhou, China.

Temperature is closely associated with respiratory disease (RD) in children, but few studies have examined whether the relationship between ambient temperature and RD in children changed after the COVID-19 epidemic. The aim of this study was to assess the relationship between temperature and RD in children after the COVID-19 epidemic in Guangzhou, China. We used a distributed lag nonlinear model to compare the relationship between temperature and RD among children in Guangzhou from 2018 to 2022. The results showed an S-shaped relationship between temperature and RD in the post-COVID-19 period with a reference minimum risk at a temperature of 21 °C and an increasing relative risk (RR) at extremely low temperature (ELT) and extremely high temperature (EHT). The highest RR associated with EHT was 1.935 (95% confidence interval [CI]: 1.314-2.850) at a lag of 0-14 days. The on-the-day lag effects were found to be strongest at the lag 0 day of EHT with a RR of 1.167 (95% CI: 1.021-1.334). Furthermore, each 1 °C increase in post-COVID-19 temperature increased the risk of RD by 8.2% (95% CI: 1.044-1.121). Our study provides evidence that the relationship between temperature and RD in children in Guangzhou changed after the COVID-19 epidemic, and high temperature is more likely to cause RD in children. Relevant government departments and parents should understand the relationship between temperature and RD in children and develop new preventive measures.

Hospital admission and mortality rates for non-COVID-19 respiratory diseases in Brazil's public health system during the covid-19 pandemic: a nationwide observational study.

OBJECTIVE: To assess the influence of the COVID-19 pandemic on hospital admissions (HA), intra-hospital deaths (HD), and intra-hospital lethality rates (HL) related to respiratory diseases (RD) other than COVID-19 in Brazil. METHODS: This observational time-series study was conducted through comparative analyses of the HA, HD, and HL related to non-COVID-19 RD registered between March and December 2020 by the Brazilian Unified Public Health System on the DataSUS Tabnet platform, using as reference the values recorded in the same period of 2019 and those projected by linear regression methods for 2020, considering the period from 2015 to 2019. The adopted statistical significance level was 5% (p < 0.05). RESULTS: Compared to 2019, in 2020, there was a 42% decrease in HA and a 7.4% decrease in total HD related to non-COVID-19 RD, followed by a 60% increase in HL associated with this group of diseases. The HA and HL registered in 2020 differed significantly from the projected trend for that year by linear regression (p < 0.05). Of note, a significant reduction in hospitalizations due to asthma (-46%), chronic obstructive pulmonary disease (-45%), bronchiectasis (-54%), pneumonia (-46%), and acute bronchitis (-73%) was observed. CONCLUSIONS: During the first 8 months of the pandemic, there was a decline in HA and an increase in HL related to non-COVID-19 RD in Brazil, which can hypothetically reflect logistical challenges and delays in the management of this group of diseases.