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The European Respiratory Journal Feb 2024Accelerated biological ageing has been associated with an increased risk of several chronic respiratory diseases. However, the associations between phenotypic age, a new...
BACKGROUND
Accelerated biological ageing has been associated with an increased risk of several chronic respiratory diseases. However, the associations between phenotypic age, a new biological age indicator based on clinical chemistry biomarkers, and common chronic respiratory diseases have not been evaluated.
METHODS
We analysed data from 308 592 participants at baseline in the UK Biobank. The phenotypic age was calculated from chronological age and nine clinical chemistry biomarkers, including albumin, alkaline phosphatase, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red cell distribution width and white blood cell count. Furthermore, phenotypic age acceleration (PhenoAgeAccel) was calculated by regressing phenotypic age on chronological age. The associations of PhenoAgeAccel with incident common chronic respiratory diseases and cross-sectional lung function were investigated. Moreover, we constructed polygenic risk scores and evaluated whether PhenoAgeAccel modified the effect of genetic susceptibility on chronic respiratory diseases and lung function.
RESULTS
The results showed significant associations of PhenoAgeAccel with increased risk of idiopathic pulmonary fibrosis (IPF) (hazard ratio (HR) 1.52, 95% CI 1.45-1.59), COPD (HR 1.54, 95% CI 1.51-1.57) and asthma (HR 1.18, 95% CI 1.15-1.20) per 5-year increase and decreased lung function. There was an additive interaction between PhenoAgeAccel and the genetic risk for IPF and COPD. Participants with high genetic risk and who were biologically older had the highest risk of incident IPF (HR 5.24, 95% CI 3.91-7.02), COPD (HR 2.99, 95% CI 2.66-3.36) and asthma (HR 2.07, 95% CI 1.86-2.31). Mediation analysis indicated that PhenoAgeAccel could mediate 10∼20% of the associations between smoking and chronic respiratory diseases, while ∼10% of the associations between particulate matter with aerodynamic diameter <2.5 µm and the disorders were mediated by PhenoAgeAccel.
CONCLUSION
PhenoAgeAccel was significantly associated with incident risk of common chronic respiratory diseases and decreased lung function and could serve as a novel clinical biomarker.
Topics: Humans; Incidence; UK Biobank; Biological Specimen Banks; Cross-Sectional Studies; Prospective Studies; Respiration Disorders; Asthma; Idiopathic Pulmonary Fibrosis; Aging; Biomarkers; Pulmonary Disease, Chronic Obstructive; Risk Factors
PubMed: 38061785
DOI: 10.1183/13993003.01720-2023 -
Medicina (Kaunas, Lithuania) Aug 2023Obstructive sleep apnea syndrome (OSAS) is the most common breathing-related sleep disorder. It is characterized by recurrent episodes of partial or complete airway... (Review)
Review
Obstructive sleep apnea syndrome (OSAS) is the most common breathing-related sleep disorder. It is characterized by recurrent episodes of partial or complete airway obstruction during sleep, resulting in a reduction in or the total cessation of airflow, despite ongoing respiratory efforts, leading to oxygen desaturation and arousal. The purpose of this literature review is to evaluate the most common characteristics of this pathology, as well as to investigate the most effective treatment options, providing an update on the management of OSA patients.
Topics: Humans; Sleep; Sleep Apnea, Obstructive
PubMed: 37629749
DOI: 10.3390/medicina59081459 -
JAMA Dec 2023The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown.
OBJECTIVES
To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial enrolling 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (AHI) less than 3 enrolled at 7 US academic sleep centers from June 29, 2016, to February 1, 2021, and followed up for 12 months.
INTERVENTION
Participants were randomized 1:1 to either early adenotonsillectomy (n = 231) or watchful waiting (n = 228).
MAIN OUTCOMES AND MEASURES
The 2 primary outcomes were changes from baseline to 12 months for caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T score, a measure of executive function; and a computerized test of attention, the Go/No-go (GNG) test d-prime signal detection score, reflecting the probability of response to target vs nontarget stimuli. Twenty-two secondary outcomes included 12-month changes in neurodevelopmental, behavioral, quality of life, sleep, and health outcomes.
RESULTS
Of the 458 participants in the analyzed sample (231 adenotonsillectomy and 237 watchful waiting; mean age, 6.1 years; 230 female [50%]; 123 Black/African American [26.9%]; 75 Hispanic [16.3%]; median AHI, 0.5 [IQR, 0.2-1.1]), 394 children (86%) completed 12-month follow-up visits. There were no statistically significant differences in change from baseline between the 2 groups in executive function (BRIEF GEC T-scores: -3.1 for adenotonsillectomy vs -1.9 for watchful waiting; difference, -0.96 [95% CI, -2.66 to 0.74]) or attention (GNG d-prime scores: 0.2 for adenotonsillectomy vs 0.1 for watchful waiting; difference, 0.05 [95% CI, -0.18 to 0.27]) at 12 months. Behavioral problems, sleepiness, symptoms, and quality of life each improved more with adenotonsillectomy than with watchful waiting. Adenotonsillectomy was associated with a greater 12-month decline in systolic and diastolic blood pressure percentile levels (difference in changes, -9.02 [97% CI, -15.49 to -2.54] and -6.52 [97% CI, -11.59 to -1.45], respectively) and less progression of the AHI to greater than 3 events/h (1.3% of children in the adenotonsillectomy group compared with 13.2% in the watchful waiting group; difference, -11.2% [97% CI, -17.5% to -4.9%]). Six children (2.7%) experienced a serious adverse event associated with adenotonsillectomy.
CONCLUSIONS
In children with mild SDB, adenotonsillectomy, compared with watchful waiting, did not significantly improve executive function or attention at 12 months. However, children with adenotonsillectomy had improved secondary outcomes, including behavior, symptoms, and quality of life and decreased blood pressure, at 12-month follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02562040.
Topics: Child; Female; Humans; Polysomnography; Quality of Life; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Snoring; Tonsillectomy; Male; Adenoidectomy; Watchful Waiting; Child, Preschool; Treatment Outcome; Follow-Up Studies
PubMed: 38051326
DOI: 10.1001/jama.2023.22114 -
JAMA Network Open Dec 2023Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies...
IMPORTANCE
Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed.
OBJECTIVE
To assess the global burden of COPD through 2050, considering COPD risk factors.
DESIGN, SETTING, AND PARTICIPANTS
In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database.
MAIN OUTCOMES AND MEASURES
To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region.
RESULTS
The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050.
CONCLUSIONS AND RELEVANCE
In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.
Topics: Male; Humans; Female; Pulmonary Disease, Chronic Obstructive; Air Pollution; Respiration Disorders; Prevalence; Smoking
PubMed: 38060225
DOI: 10.1001/jamanetworkopen.2023.46598 -
BMC Pulmonary Medicine Jul 2023Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain...
BACKGROUND
Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain whether GERD causally influences these diseases. In this study, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases.
METHODS
88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings.
RESULTS
Our study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25-1.56, P < 0.001), idiopathic pulmonary fibrosis (IPF) (OR 1.43, 95%CI 1.05-1.95, P = 0.022), chronic obstructive disease (COPD) (OR 1.64, 95%CI 1.41-1.93, P < 0.001), chronic bronchitis (OR 1.77, 95%CI 1.15-2.74, P = 0.009), while no correlation was observed for bronchiectasis (OR 0.93, 95%CI 0.68-1.27, P = 0.645). Additionally, GERD was associated with 12 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered.
CONCLUSIONS
Our study suggested that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, indicating that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases.
Topics: Humans; Bronchitis, Chronic; Genome-Wide Association Study; Mendelian Randomization Analysis; Gastroesophageal Reflux; Asthma; Respiration Disorders; Idiopathic Pulmonary Fibrosis
PubMed: 37403021
DOI: 10.1186/s12890-023-02502-8 -
Sleep & Breathing = Schlaf & Atmung Dec 2023The purpose of this study is to examine the pathophysiology underlying sleep apnea (SA). (Review)
Review
OBJECTIVE
The purpose of this study is to examine the pathophysiology underlying sleep apnea (SA).
BACKGROUND
We consider several critical features of SA including the roles played by the ascending reticular activating system (ARAS) that controls vegetative functions and electroencephalographic findings associated with both SA and normal sleep. We evaluate this knowledge together with our current understanding of the anatomy, histology, and physiology of the mesencephalic trigeminal nucleus (MTN) and mechanisms that contribute directly to normal and disordered sleep. MTN neurons express γ-aminobutyric acid (GABA) receptors which activate them (make chlorine come out of the cells) and that can be activated by GABA released from the hypothalamic preoptic area.
METHOD
We reviewed the published literature focused on sleep apnea (SA) reported in Google Scholar, Scopus, and PubMed databases.
RESULTS
The MTN neurons respond to the hypothalamic GABA release by releasing glutamate that activates neurons in the ARAS. Based on these findings, we conclude that a dysfunctional MTN may be incapable of activating neurons in the ARAS, notably those in the parabrachial nucleus, and that this will ultimately lead to SA. Despite its name, obstructive sleep apnea (OSA) is not caused by an airway obstruction that prevents breathing.
CONCLUSIONS
While obstruction may contribute to the overall pathology, the primary factor involved in this scenario is the lack of neurotransmitters.
Topics: Humans; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration; Sleep; gamma-Aminobutyric Acid
PubMed: 36976413
DOI: 10.1007/s11325-023-02783-7 -
Clinical Medicine (London, England) Jan 2024Hypercapnia is commonly encountered by general and specialist respiratory clinicians. Patients at risk of developing hypercapnic respiratory failure include those with... (Review)
Review
Hypercapnia is commonly encountered by general and specialist respiratory clinicians. Patients at risk of developing hypercapnic respiratory failure include those with chronic obstructive pulmonary disease (COPD), obesity and neuromuscular disease. Such patients may present to clinicians acutely unwell on the acute medical take or during an inpatient deterioration, or be identified in the stable outpatient setting. In this review, we provide a practical guide to develop clinicians' knowledge, skills and confidence in promptly recognising and managing hypercapnic respiratory failure, and to promote national ventilation quality standards to encourage consistent delivery of high-quality care and optimise outcomes for patients.
Topics: Humans; Hypercapnia; Inpatients; Obesity; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency
PubMed: 38382181
DOI: 10.1016/j.clinme.2023.100007 -
Heart & Lung : the Journal of Critical... 2023Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or...
INTRODUCTION
Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or muscle weakness. However, whether and to what extent symptom burden differs between patients with IPF or sarcoidosis and individuals without respiratory disease remains currently unknown.
OBJECTIVES
To study the respiratory and non-respiratory burden of multiple symptoms in patients with IPF or sarcoidosis and to compare the symptom burden with individuals without impaired spirometric values, FVC and FEV1 (controls).
METHODS
Demographics and symptoms were assessed in 59 patients with IPF, 60 patients with sarcoidosis and 118 controls (age ≥18 years). Patients with either condition were matched to controls by sex and age. Severity of 14 symptoms was assessed using a Visual Analogue Scale.
RESULTS
44 patients with IPF (77.3% male; age 70.6±5.5 years) and 44 matched controls, and 45 patients with sarcoidosis (48.9% male; age 58.1±8.6 year) and 45 matched controls were analyzed. Patients with IPF scored higher on 11 symptoms compared to controls (p<0.05), with the largest differences for dyspnoea, cough, fatigue, muscle weakness and insomnia. Patients with sarcoidosis scored higher on all 14 symptoms (p<0.05), with the largest differences for dyspnoea, fatigue, cough, muscle weakness, insomnia, pain, itch, thirst, micturition (night, day).
CONCLUSIONS
Generally, respiratory and non-respiratory symptom burden is significantly higher in patients with IPF or sarcoidosis compared to controls. This emphasizes the importance of awareness for respiratory and non-respiratory symptom burden in IPF or sarcoidosis and the need for additional research to study the underlying mechanisms and subsequent interventions.
Topics: Humans; Male; Adolescent; Aged; Middle Aged; Female; Cough; Sleep Initiation and Maintenance Disorders; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Dyspnea; Fatigue; Muscle Weakness
PubMed: 37269615
DOI: 10.1016/j.hrtlng.2023.05.013 -
Current Opinion in Critical Care Oct 2023Disparities are common within healthcare, and critical illness is no exception. This review summarizes recent literature on health disparities within respiratory... (Review)
Review
PURPOSE OF REVIEW
Disparities are common within healthcare, and critical illness is no exception. This review summarizes recent literature on health disparities within respiratory failure, focusing on race, ethnicity, socioeconomic status, and sex.
RECENT FINDINGS
Current evidence indicates that Black patients have higher incidence of respiratory failure, while the relationships among race, ethnicity, and mortality remains unclear. There has been renewed interest in medical device bias, specifically pulse oximetry, for which data demonstrate patients with darker skin tones may be at risk for undetected hypoxemia and worse outcomes. Lower socioeconomic status is associated with higher mortality, and respiratory failure can potentiate socioeconomic inequities via illness-related financial toxicity. Literature on sex-based disparities is limited; however, evidence suggests males receive more invasive care, including mechanical ventilation.
SUMMARY
Most studies focused on disparities in incidence and mortality associated with respiratory failure, but few relied on granular clinical data of patients from diverse backgrounds. Future studies should evaluate processes of care for respiratory failure that may mechanistically contribute to disparities in order to develop interventions that improve outcomes.
Topics: Male; Humans; Respiration, Artificial; Respiratory Insufficiency
PubMed: 37641499
DOI: 10.1097/MCC.0000000000001079 -
JAMA Sep 2023The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.
OBJECTIVE
To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age.
DESIGN, SETTING, AND PARTICIPANTS
Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022.
INTERVENTIONS
Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment.
MAIN OUTCOMES AND MEASURES
The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years.
RESULTS
Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]).
CONCLUSIONS AND RELEVANCE
In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12611000916943.
Topics: Female; Humans; Infant; Infant, Newborn; Dyspnea; Follow-Up Studies; Infant, Premature; Lipoproteins; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Sounds; Surface-Active Agents; Catheterization; Minimally Invasive Surgical Procedures; Continuous Positive Airway Pressure; Male; Child, Preschool
PubMed: 37695601
DOI: 10.1001/jama.2023.15694