Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update.

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with "mild" asthma) as combination ICS-formoterol taken as needed for symptom relief. For patients with moderate-severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS-formoterol. Asthma treatment is not "one size fits all"; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.

Effect of Weight Loss and Continuous Positive Airway Pressure on Obstructive Sleep Apnea and Metabolic Profile Stratified by Craniofacial Phenotype: A Randomized Clinical Trial.

Rationale: Craniofacial structure is believed to modulate the effect of weight loss on obstructive sleep apnea (OSA), but whether this affects metabolic profile after weight loss compared with continuous positive airway pressure (CPAP) is unknown among obese Chinese patients with OSA. Objectives: To compare the change in metabolic profile between a lifestyle modification program (LMP), stratified by craniofacial phenotype, and CPAP therapy for 6 months. Methods: We randomly assigned 194 patients with body mass index ⩾ 25 kg/m2 and moderate to severe OSA to participate in the LMP or receive CPAP therapy for 6 months in a 2:1 ratio. Assessments included computed tomography for assessing maxillomandibular volume (MMV), hsCRP (high-sensitivity C-reactive protein), and insulin sensitivity. Measurements and Main Results: Among 128 and 66 subjects in the LMP and CPAP groups, respectively, hsCRP was reduced more in the LMP group than the CPAP group (median [interquartile range], -0.7 [-1.4 to -0.0] vs. -0.3 [-0.9 to 0.4] mg/L; P = 0.012). More patients in the LMP group achieved low hsCRP (<1 mg/L) than the CPAP group (21.1% vs. 9.1%; P = 0.04). Insulin sensitivity improved only in the LMP group, with 3.1 (95% confidence interval, 1.5-6.6) times more patients with normal glucose regulation after intervention. The LMP group was stratified into LMP-small MMV (n = 64) and LMP-large MMV (n = 64) groups according to the median MMV value of 233.2 cm3. There was no significant difference in hsCRP (median [interquartile range], -0.7 [-1.3 to 0.1] vs. -0.7 [-1.5 to -0.2] mg/L; P = 0.884) and insulin sensitivity (median [interquartile range], 0.5 [-0.2 to 1.9] vs. 0.6 [0.1 to 2.0]; P = 0.4860) between the LMP-small MMV and LMP-large MMV groups. Conclusions: Weight reduction alleviated subclinical inflammation and improved insulin sensitivity more than CPAP among obese Chinese patients with moderate to severe OSA, and this effect was not influenced by craniofacial structure. Clinical trial registered with www.clinicaltrials.gov (NCT03287973).

Continuous Positive Airway Pressure Does Not Improve Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea. A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H2O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H2O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with SaO2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.

Real-Time Monitoring of the Effects of Personal Temperature Exposure on the Blood Oxygen Saturation Level in Elderly People with and without Chronic Obstructive Pulmonary Disease: A Panel Study in Hong Kong.

Few studies have investigated the short-term effect of personal temperature exposure on blood oxygen saturation (SpO2). We conducted this longitudinal panel study with real-time monitoring of SpO2 and environmental exposure for 3 continuous days for 20 patients with chronic obstructive pulmonary disease (COPD) and 20 healthy volunteers in Hong Kong, to explore the time course (from minutes to hours) of change in SpO2 in response to temperature in elderly people. We employed a generalized additive mixed model to evaluate the acute effects of personal temperature exposure on changes in SpO2 and risk of oxygen desaturation while adjusting for seasonality, environmental co-exposures, and personal characteristics. We observed a concurrent decline in SpO2 by 0.27% (95% confidence interval [CI]: 0.22-0.32%) and an increase in the risk of oxygen desaturation by an OR of 1.14 (95% CI, 1.10-1.18) associated with a 1 °C increase in personal temperature, and the association lasted over several hours. Results showed that the decline in SpO2 in elderly people was associated with an increase in personal temperature exposure within minutes to hours, particularly in women and male patients with COPD. Temperature-induced oxygen desaturation may play a pivotal role in COPD exacerbation.

Time course of blood oxygen saturation responding to short-term fine particulate matter among elderly healthy subjects and patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) often experience deteriorating gaseous exchange which in turn may result in declines in blood oxygen saturation (SpO2). Increasing evidence has also shown that elevated levels of fine particulate matter (PM2.5) may contribute to COPD pathogenesis. However, the acute effects of PM2.5 on SpO2 among COPD patients remain unclear, especially for its time course. Therefore, we conducted this panel study with 3-day real-time monitoring for personal PM2.5 exposure and concurrent SpO2 of 39 participants (20 COPD patients, 19 healthy participants), aged 60 to 90 years, in Hong Kong to explore the acute effects of personal PM2.5 exposure on SpO2 (within minutes to hours). We applied a linear mixed effect model to examine the associations between personal PM2.5 and SpO2, while adjusting for temporal trend, personal characteristics, weather conditions, and co-exposure to gaseous pollutants (ambient ozone, nitrogen dioxides, carbon monoxide, and atmospheric pressure). We found that short-term exposure to PM2.5 might result in acute declines of SpO2 within minutes, and the effects would last for several hours. An interquartile range increase of personal PM2.5 exposure (17.2 µg/m3) was associated with -0.19% (95% CI: -0.26% to -0.12%) changes of concurrent SpO2 for all participants. The most significant decline was observed at lag0-3 h, and then became insignificant at lag0-12 h. At lag0-1 h, estimated mean changes of SpO2 were -0.40% (95% CI: -0.55% to -0.24%) for COPD patients and -0.09% (95% CI: -0.23% to 0.06%) for healthy participants. Compared with healthy participants, the effects of PM2.5 exposure on SpO2 for COPD patients were slightly stronger and more acute. Reducing PM2.5 concentrations might be a useful approach to improve health status and reduce exacerbations for COPD patients.

Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations.

BACKGROUND AND OBJECTIVE: Airway inflammation accompanying exacerbations varies among individuals with some having neutrophilic, while others showing eosinophilic inflammation. This study assessed the cut-off values of blood eosinophil count for identifying subjects with longer hospital length of stay (LOS) with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: Patients were recruited at presentation to the hospital with an AECOPD. Complete blood picture with differential count was taken on admission. Patients were treated with a standard course of systemic corticosteroid and antibiotic and evaluated at 8 weeks post-exacerbation for lung function measurement and 6-min walk. They were followed up in 1 year for any readmissions or mortality. Cut-off values of eosinophils for assessment of longer LOS were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 346 patients with admission eosinophil count were included in the analysis (333 (96.2%) were males; mean ± SD age: 74.9 ± 7.8 years; mean forced expiratory volume in 1 s (FEV1 ): 43.4 ± 16.3% predicted). The median (interquartile range (IQR)) of the absolute peripheral eosinophil count, percent eosinophil count and LOS were 0.11 (0.25) × 109 /L, 1 (3) % and 5 (7) days, respectively. Using the median LOS of ≥5 days as the cut-off, ROC analysis of the cut-off value of eosinophil count associated with longer LOS was at <2% (area under the curve (AUC): 0.666, P < 0.001) while absolute eosinophil count was at <0.144 × 109 /L (AUC: 0.645, P < 0.001). These eosinophil cut-off values could predict longer LOS independent of age, lung function and previous hospital admissions, but had no association with readmissions for AECOPD and mortality at 12 months. CONCLUSION: An eosinophil value of <0.144 × 109 /L on admission or <2% was associated with longer hospital LOS for AECOPD.

Continuous positive airway pressure for obstructive sleep apnoea does not improve asthma control.

BACKGROUND AND OBJECTIVE: Unrecognized obstructive sleep apnoea syndrome (OSAS) may lead to poor asthma control despite optimal therapy. We assessed asthma control, airway responsiveness, daytime sleepiness and health status at baseline and 3 months after continuous positive airway pressure (CPAP) treatment among asthma patients with nocturnal symptoms and OSAS. METHODS: Patients with nocturnal asthma symptoms despite receiving at least moderate-dose inhaled corticosteroid and long-acting bronchodilators underwent a home sleep study using 'Embletta' portable diagnostic system. Patients with significant OSAS (apnoea-hypopnoea index (AHI) ≥10/h) were randomized to receive either CPAP or conservative treatment for 3 months. RESULTS: Among 145 patients recruited, 122 underwent sleep study with 41 (33.6%) having AHI ≥10/h. Patients with significant OSAS had higher BMI (27.4 (5.1) vs 25.1 (4.5) kg/m2 , P = 0.016), bigger neck circumference (36.6 (3.1) vs 34.8 (3.6) cm, P = 0.006) and lower minimum SaO2 (80.7 (6.6) vs 87.2 (3.9) %, P < 0.001). Using intention-to-treat analysis among 37 patients with AHI ≥10/h (CPAP group (n = 17) vs control group (n = 20)), there was no significant difference in Asthma Control Test score (CPAP 3.2 (2.7) vs control 2.4 (5.7), P = 0.568) but the CPAP group had a greater improvement in Epworth Sleepiness Scale (-3.0 (4.5) vs 0.5(3.8), P = 0.014), Asthma Quality of Life Questionnaire (0.6 (0.8) vs 0.02 (0.7), P = 0.022) and vitality domain in the SF-36 questionnaire (14.7 (16.8) vs 0.3 (16.2), P = 0.012) after 3 months. Data are presented as mean (SD) unless otherwise stated. CONCLUSION: A high prevalence of OSAS was found among patients with asthma and snoring. CPAP therapy for 3 months did not enhance asthma control but improved daytime sleepiness, quality of life and vitality.

Effects of CPAP therapy on visceral fat thickness, carotid intima-media thickness and adipokines in patients with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is associated with an increased prevalence of metabolic syndrome. This study explores the effects of continuous positive airway pressure (CPAP) for patients with OSA on visceral and mesenteric fat thickness, carotid intima-media thickness (IMT) and adipokines. METHODS: A randomized controlled study was conducted at a teaching hospital on 90 patients newly diagnosed with OSA to receive either therapeutic CPAP or subtherapeutic CPAP for 3 months. Visceral fat thickness and carotid IMT were measured with B-mode ultrasound; adipokine levels were assessed at baseline and 3 months. RESULTS: Altogether, 45 patients received therapeutic CPAP and 45 received subtherapeutic CPAP without significant differences in age 50.3 (10.1) versus 48.7 (9.0) years, BMI 28.2 (3.9) versus 28.2 (4.5) kg/m2 , Epworth Sleepiness Scale (ESS) 12.4 (5.9) versus 11.3 (4.7), apnoea-hypopnoea index (AHI) 30.6 (21.4) versus 35.2 (25.5) /h, minimum SaO2 79.6 (10.8) versus 76.7 (12.4) % and existing co-morbidities. CPAP usage was therapeutic 4.2 (2.1) versus subtherapeutic 4.1 (2.0) h/night over 3 months. Adiponectin and irisin levels changed significantly following therapeutic CPAP for 3 months versus subtherapeutic CPAP (-1.6 vs 7.3, P = 0.042; 0.1 vs -0.1, P = 0.028 respectively) while only serum level of monocyte chemotactic protein 1 (MCP-1) at baseline was positively correlated with AHI (r = 0.278). No significant changes were observed in other adipokines, visceral fat thickness and IMT. CONCLUSION: Short-term therapeutic CPAP versus subtherapeutic CPAP does not significantly reduce visceral fat thickness and IMT, although it reduces adiponectin and increases irisin.

Comprehensive care programme for patients with chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: There have been no randomised controlled trials that specifically evaluate the effect of a comprehensive programme with multidisciplinary input on patients who have just been discharged from hospital after treatment of acute exacerbation of COPD (AECOPD). The aim of this study was to assess whether a comprehensive care programme would decrease hospital readmissions and length of hospital stay (LOS) for patients with COPD. METHODS: Patients discharged from hospital after an episode of AECOPD were randomised to an intervention group (IG) or usual care group (UG). The IG received a comprehensive, individualised care plan which included education from a respiratory nurse, physiotherapist support for pulmonary rehabilitation, 3-monthly telephone calls by a respiratory nurse over 1 year, and follow-up at a respiratory clinic with a respiratory specialist once every 3 months for 1 year. The UG were managed according to standard practice. The primary outcome was hospital readmission rate at 12 months. RESULTS: 180 patients were recruited (IG, N=90; UG, N=90; mean±SD age 74.7±8.2 years, 172 (95.6%) men; mean±SD FEV1 45.4±16.6% predicted). At 12 months, the adjusted relative risk of readmission was 0.668 (95% CI 0.449 to 0.995, p=0.047) for the IG compared with the UG. At 12 months, the IG had a shorter LOS (4.59±7.16 vs 8.86±10.24 days, p≤0.001), greater improvement in mean Modified Medical Research Council Dyspnoea Scale (-0.1±0.6 vs 0.2±0.6, p=0.003) and St George's Respiratory Questionnaire score (-6.9±15.3 vs -0.1±13.8, p=0.003) compared with the UG. CONCLUSIONS: A comprehensive COPD programme can reduce hospital readmissions for COPD and LOS, in addition to improving symptoms and quality of life of the patients. TRIAL REGISTRATION NUMBER: NCT 01108835, Results.

Undiagnosed airflow limitation is common in patients with coronary artery disease and associated with cardiac stress.

BACKGROUND AND OBJECTIVE: Smoking is a common risk factor for coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We evaluated the prevalence of undiagnosed COPD in patients with CAD and assessed the relationship between airflow obstruction and markers of cardiac stress. METHODS: We recruited prospectively consecutive patients aged >40 years without known history of chronic lung disease (e.g. asthma, COPD, bronchiectasis) who had undergone percutaneous coronary intervention (PCI) for obstructive CAD between August 2009 and October 2010. Spirometry was performed and serum ST2, a novel biomarker of cardiomyocyte stress and fibrosis, was measured by enzyme-linked immunosorbent assay. RESULTS: Among 475 subjects (mean age 64 ± 9.7, range 42-85 years, 87.2% males, 58.5% current or ex-smokers) who underwent spirometry, 51 (10.7%) had undiagnosed airflow obstruction with FEV1 /FVC ratio <70%. Of these 51 subjects, 14 (2.9%), 23 (4.8%) and 14 (2.9%) had FEV1 ≥80, 50-80 and 30-50% predicted normal, respectively. ST2 level was measured in all the subjects with undiagnosed airflow obstruction and in 290 subjects with normal lung function. There was no significant difference in left ventricular ejection fraction on echocardiogram between subjects with and without airflow obstruction. Patients with severe airflow obstruction had a higher level of cardiac stress marker ST2 than those with mild and moderate airflow obstruction (rho = -0.214, P ≤ 0.001). CONCLUSION: Undiagnosed airflow obstruction is common among patients with CAD who have undergone PCI. Severity of airflow limitation is associated with increasing cardiac stress.

Mesenteric fat thickness is associated with metabolic syndrome independently of Apnoea-Hypopnoea Index in subjects with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Mesenteric fat thickness (MFT) was associated with metabolic syndrome (MetS) and obstructive sleep apnoea (OSA) in separate studies. This study aimed to assess whether the association of MFT with MetS was independent of OSA in subjects with suspected OSA. METHODS: Two hundred forty-two subjects (men: 181; women: 61) with suspected OSA underwent ultrasound examinations for measurements of mesenteric, subcutaneous and preperitoneal fat thicknesses after overnight polysomnography. Anthropometric measurements and metabolic risk profile were assessed. RESULTS: Two hundred twenty-one (91%) subjects were confirmed to have OSA with Apnoea-Hypopnoea Index (AHI) >5/h. MFT had significant correlation (P < 0.01) with AHI and most MetS components. In partial correlation with adjustment for AHI, MFT had significant correlation (P < 0.01) with most MetS components including fasting plasma glucose (r = 0.25), triglycerides (r = 0.24), HDL cholesterol (r = -0.29) and waist circumference (r = 0.56). In multivariate logistic regression with adjustments for the confounding variables including AHI, MFT was the only variable independently associated with MetS, with the odds ratio of 5.48 (95% CI: 1.5-20.0) for every 1 cm increase of MFT. When the subjects were subdivided into obese (BMI ≥ 27.5 kg/m(2) ) and non-obese (BMI < 27.5 kg/m(2) ) groups, the positive association of MFT with MetS persisted in the non-obese group only, with the odds ratio of 22 (95% CI 2.8-174.1) for every 1 cm increase of MFT. The AHI had significant association with MetS in male subjects only. CONCLUSION: MFT, rather than AHI, is the major independent determinant of MetS in subjects with suspected OSA, particularly in non-obese subjects. See Editorial, page 408.

Suicidal ideation in Chinese patients with chronic obstructive pulmonary disease: a controlled study.

BACKGROUND: No study has been published on the prevalence of suicidal behaviour in older Chinese patients with chronic obstructive pulmonary disease (COPD). This study examined the 1-year prevalence of suicidal ideation in older Chinese COPD patients and explored its demographic and clinical correlates. METHODS: A consecutive sample of 143 COPD patients and 211 matched control subjects were recruited and interviewed using structured, standardized instruments. RESULTS: The 1-year prevalence of suicidal ideation in COPD patients and controls were 15.4% and 10.9%, respectively. In multivariate analyses, suicidal ideation was significantly associated with the severity of depressive symptoms in COPD patients. CONCLUSION: Suicidal ideation was not higher in COPD patients than in controls.