Performance of triggers in detecting hospitalizations related to drug-induced respiratory disorders in older adults: A pilot cross-sectional study.

BACKGROUND: There is no gold-standard trigger for detecting drug-induced respiratory disorders, a type of Adverse Drug Event (ADE) with high morbimortality, particularly in older people. OBJECTIVE: To propose and evaluate the performance of triggers for detecting hospitalizations related to drug-induced respiratory disorders in older people. METHODS: A pilot cross-sectional study was conducted with older people (age ≥ 60) admitted to a Brazilian hospital. Electronic chart documentation was screened using ICD-10 codes; Global Trigger Tool (GTT); and drugs potentially associated with respiratory disorders. A chart and medication review were conducted to perform the causality assessment using the instrument developed by the World Health Organization. The performance of triggers was evaluated by the Positive Predictive Value (PPV), with values ≥ 0.20 indicating good performance. RESULTS: Among 221 older people, 72 were eligible. Potential drug-induced dyspnea and/or cough were detected in six older people (6/72), corresponding to a prevalence of 8.3 %. The overall PPV of the triggers was 0.14, with abrupt medication stop (PPV = 1.00), codeine (PPV = 1.00), captopril (PPV = 0.33), and carvedilol (PPV = 0.33) showing good performance. Two triggers were proposed for detecting therapeutic ineffectiveness associated with respiratory disorders: furosemide (PPV = 0.23) and prednisone (PPV = 0.20). CONCLUSION: The triggers enabled the identification that one in 12 hospitalizations was related to drug-induced respiratory. Although good performance was observed in the application of triggers, additional investigations are needed to assess the feasibility of incorporating them into clinical practice for the screening, detection, management, and reporting of these ADEs, which are considered to be underreported and difficult to detect.

CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders.

Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.

Quantification of breathing irregularity for the diagnosis of dysfunctional breathing using proportional tidal volume variation: a cross-sectional, retrospective real-world study.

OBJECTIVES: To develop a statistical approach that provides a quantitative index measuring the magnitude of the irregularity of the breathing response to exercise for the diagnosis of dysfunctional breathing. DESIGN: Cross-sectional, retrospective, real-world study. SETTING: Single-centre study. PARTICIPANTS: A population of 209 patients investigated with cardiopulmonary exercise testing in our institution for unexplained or disproportionate exertional dyspnoea between January and July 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: A novel statistical approach providing a quantitative index-proportional tidal volume variation (PTVV)-was developed to measure the magnitude of the irregularity of the breathing response to exercise. RESULTS: PTVV provided a reliable statistical readout for the objective assessment of DB with a prediction accuracy of 78% (95% CI: 72 to 83%). The prevalence of DB in the investigated population was high with more than half of the patients affected by moderate-to-severe DB. CONCLUSIONS: PTVV can easily be implemented in the clinical routine. Our study suggests a possible further simplification for the diagnosis of DB with two objective criteria including PTVV and one single criterion for hyperventilation.

Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases.

Dysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60-9.84) and asthma (OR = 0.82, 95% CI = 0.74-0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a Delphi approach.

BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 over 2017-2022 in Sanandaj, an area of Iran.

The risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 has been less investigated. In this study, the attributable risk was estimated in an area of Iran. The predicted air PM2.5 using satellite data and a two-stage regression model was used as the predictor of the diseases. The dose-response linkage between the bias-corrected predictor employing a strong statistical approach and the outcomes was evaluated using the distributed lag nonlinear model. We considered two distinct scenarios of PM2.5 for the risk estimation. Alongside the risk, the attributable risk and number were estimated for different levels of PM2.5 by age and gender categories. The cumulative influence of PM2.5 particles on respiratory illnesses was statistically significant at 13-16 µg/m3 relative to the reference value (median), mostly apparent in the middle delays. The cumulative relative risk of 90th and 95th percentiles were 2.03 (CI 95%: 1.28, 3.19) and 2.25 (CI 95%: 1.28, 3.96), respectively. Nearly 600 cases of the diseases were attributable to the non-optimum values of the pollutant during 2017-2022, of which more than 400 cases were attributed to high values range. The predictor's influence on cardiovascular illnesses was along with uncertainty, indicating that additional research into their relationship is needed. The bias-corrected PM2.5 played an essential role in the prediction of respiratory illnesses, and it may likely be employed as a trigger for a preventative strategy.

Impact of pulmonary rehabilitation on patients with different chronic respiratory diseases during hospitalization.

The impact of pulmonary rehabilitation (PR) on patients with different chronic respiratory diseases (CRDs) during hospitalization has not been thoroughly evaluated before. The objectives of the current research were to assess the effect of comprehensive PR management on inpatients' self-management skills, exercise capacity, nutrition assessment and mental health issues and explore whether impacts of PR vary in different CRDs. This retrospective study analyzed the clinical data from 272 inpatients with CRDs receiving PR management during hospitalization between October 2020 and March 2022 in Beijing Chao-Yang Hospital. Significant improvements were found in the patients' ability of daily living (ADL), dyspnea (assessed by modified medical research council dyspnea scale (MMRC)), handgrip strength, maximal inspiratory and expiratory pressure, anxiety (using the 7-item generalized anxiety disorder scale (GAD-7)) and depression (the 9-item patient health questionnaire score (PHQ-9)). There was no significant change in nutrition assessment pre-post PR management during hospitalization. The subgroup analyses were conducted on hospitalized patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, interstitial lung diseases (ILDs) and other CRDs (e.g., lung cancer, diaphragm hemiparesis, obesity, etc.). The results showed that ADL, MMRC score, MIP, MEP, PHQ-9 score improved in all subgroups with CRDs. Handgrip strength of left hand was increased in COPD inpatients and anxiety was improved in all subgroups except for ILDs. Comprehensive PR management was necessary and beneficial for patients with different CRDs during hospitalization.

Environmental pollutants exposure-derived extracellular vesicles: crucial players in respiratory disorders.

BACKGROUND: Individual exposure to environmental pollutants, as one of the most influential drivers of respiratory disorders, has received considerable attention due to its preventability and controllability. Considering that the extracellular vesicle (EV) was an emerging intercellular communication medium, recent studies have highlighted the crucial role of environmental pollutants derived EVs (EPE-EVs) in respiratory disorders. METHODS: PubMed and Web of Science were searched from January 2018 to December 2023 for publications with key words of environmental pollutants, respiratory disorders and EVs. RESULTS: Environmental pollutants could disrupt airway intercellular communication by indirectly stimulating airway barrier cells to secrete endogenous EVs, or directly transmitting exogenous EVs, mainly by biological pollutants. Mechanistically, EPE-EVs transferred specific contents to modulate biological functions of recipient cells, to induce respiratory inflammation and impair tissue and immune function, which consequently contributed to the development of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary hypertension, lung cancer and infectious lung diseases. Clinically, EVs could emerged as promising biomarkers and biological agents for respiratory diseases attributed by their specificity, convenience, sensibility and stability. CONCLUSIONS: Further studies of EPE-EVs are helpful to understand the aetiology and pathology of respiratory diseases, and facilitate the precision respiratory medicine in risk screening, early diagnosis, clinical management and biotherapy.

The changing health effects of air pollution exposure for respiratory diseases: a multicity study during 2017-2022.

BACKGROUND: Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. METHODS: We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. RESULTS: Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1-0.7%) and 1.4% (1.0-1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5-0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5-1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8-30.3%) and 12.7% (10.8-14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. CONCLUSIONS: Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1-59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial.

BACKGROUND: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. METHODS: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. FINDINGS: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. INTERPRETATION: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. FUNDING: SIDA Sweden and Grand Challenges Ethiopia.

Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Advances in co-pathogenesis of the united airway diseases.

According to the concept of "united airway diseases", the airway is a single organ in which upper and lower airway diseases are commonly comorbid. A range of inflammatory factors have been found to play an important role in the chain reaction of upper and lower airway diseases. However, the amount of research on this concept remains limited. The underlying mechanism of the relationship between typical diseases of the united airway, such as asthma, allergic rhinitis, and chronic sinusitis, also needs to be further explored. This review highlights the interaction between upper and lower respiratory diseases gathered from epidemiological, histoembryology, neural mechanistic, microbiological, and clinical studies, revealing the relationship between the upper and lower respiratory tracts.

Responsiveness of respiratory function in Parkinson's Disease to an integrative exercise programme: A prospective cohort study.

INTRODUCTION: Respiratory disorders are the most common cause of death in Parkinson's Disease (PD). Conflicting data exist on the aetiology of respiratory dysfunction in PD and few studies examine the effects of exercise-based interventions on respiratory measures. This study was conducted to better understand respiratory dysfunction in PD and to identify measures of dysfunction responsive to an integrative exercise programme. OBJECTIVES: The objectives were to compare baseline respiratory measures with matched, published population norms and to examine immediate and longer-term effects of a 12-week integrated exercise programme on these measures. DESIGN: Twenty-three people with mild PD (median Hoehn & Yahr = 2) self-selected to participate in this exploratory prospective cohort study. Evaluation of participants occurred at three time points: at baseline; following the 12-week exercise programme and at 4-month follow-up. OUTCOME MEASURES: Outcome measures included: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), FEV1/FVC ratio, Peak Expiratory Flow (PEF), Inspiratory Muscle Strength (MIP), Expiratory Muscle Strength (MEP), Peak Cough Flow (PCF), and Cardiovascular Fitness measures of estimated VO2 max and 6-Minute Walk Test (6MWT). RESULTS: Compared to published norms, participants had impaired cough, reduced respiratory muscle strength, FEV, FVC, PEF and cardiovascular fitness. Post exercise intervention, statistically significant improvements were noted in MEP, cardiovascular fitness, and PEF. However only gains in PEF were maintained at 4-month follow-up. CONCLUSIONS: Significant respiratory dysfunction exists, even in the early stages of PD. Metrics of respiratory muscle strength, peak expiratory flow and cardiovascular fitness appear responsive to an integrative exercise programme.