Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently recommend selective use of ICS. ICS are not recommended as monotherapy for people with COPD, and are only given in combination with long-acting bronchodilators due to greater efficacy of combination therapy. Incorporating and critiquing newly published placebo-controlled trials into the monotherapy evidence base may help to resolve ongoing uncertainties and conflicting findings about their role in this population. OBJECTIVES: To evaluate the benefits and harms of inhaled corticosteroids, used as monotherapy versus placebo, in people with stable COPD, in terms of objective and subjective outcomes. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was October 2022. SELECTION CRITERIA: We included randomised trials comparing any dose of any type of ICS, given as monotherapy, with a placebo control in people with stable COPD. We excluded studies of less than 12 weeks' duration and studies of populations with known bronchial hyper-responsiveness (BHR) or bronchodilator reversibility. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our a priori primary outcomes were 1. exacerbations of COPD and 2. quality of life. Our secondary outcomes were 3. all-cause mortality, 4. lung function (rate of decline of forced expiratory volume in one second (FEV1)), 5. rescue bronchodilator use, 6. exercise capacity, 7. pneumonia and 8. adverse events including pneumonia. ]. We used GRADE to assess certainty of evidence. MAIN RESULTS: Thirty-six primary studies with 23,139 participants met the inclusion criteria. Mean age ranged from 52 to 67 years, and females were 0% to 46% of participants. Studies recruited across the severities of COPD. Seventeen studies were of duration longer than three months and up to six months and 19 studies were of duration longer than six months. We judged the overall risk of bias as low.  Long-term (more than six months) use of ICS as monotherapy reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: rate ratio 0.88 exacerbations per participant per year, 95% confidence interval (CI) 0.82 to 0.94; I2 = 48%, 5 studies, 10,097 participants; moderate-certainty evidence; pooled means analysis: mean difference (MD) -0.05 exacerbations per participant per year, 95% CI -0.07 to -0.02; I2 = 78%, 5 studies, 10,316 participants; moderate-certainty evidence). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60; I2 = 0%; 5 studies, 2507 participants; moderate-certainty evidence; minimal clinically importance difference 4 points). There was no evidence of a difference in all-cause mortality in people with COPD (odds ratio (OR) 0.94, 95% CI 0.84 to 1.07; I2 = 0%; 10 studies, 16,636 participants; moderate-certainty evidence). Long-term use of ICS  reduced the rate of decline in FEV1 in people with COPD (generic inverse variance analysis: MD 6.31 mL/year benefit, 95% CI 1.76 to 10.85; I2 = 0%; 6 studies, 9829 participants; moderate-certainty evidence; pooled means analysis: 7.28 mL/year, 95% CI 3.21 to 11.35; I2 = 0%; 6 studies, 12,502 participants; moderate-certainty evidence). ADVERSE EVENTS: in the long-term studies, the rate of pneumonia was increased in the ICS group, compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.38, 95% CI 1.02 to 1.88; I2 = 55%; 9 studies, 14,831 participants; low-certainty evidence). There was an increased risk of oropharyngeal candidiasis (OR 2.66, 95% CI 1.91 to 3.68; 5547 participants) and hoarseness (OR 1.98, 95% CI 1.44 to 2.74; 3523 participants). The long-term studies that measured bone effects generally showed no major effect on fractures or bone mineral density over three years. We downgraded the certainty of evidence to moderate for imprecision and low for imprecision and inconsistency. AUTHORS' CONCLUSIONS: This systematic review updates the evidence base for ICS monotherapy with newly published trials to aid the ongoing assessment of their role for people with COPD. Use of ICS alone for COPD likely results in a reduction of exacerbation rates of clinical relevance, probably results in a reduction in the rate of decline of FEV1 of uncertain clinical relevance and likely results in a small improvement in health-related quality of life not meeting the threshold for a minimally clinically important difference. These potential benefits should be weighed up against adverse events (likely to increase local oropharyngeal adverse effects and may increase the risk of pneumonia) and probably no reduction in mortality. Though not recommended as monotherapy, the probable benefits of ICS highlighted in this review support their continued consideration in combination with long-acting bronchodilators. Future research and evidence syntheses should be focused in that area.

A Virtual Ward Model of Care for Patients With COVID-19: Retrospective Single-Center Clinical Study.

BACKGROUND: COVID-19 has necessitated the implementation of innovative health care models in preparation for an influx of patients. A virtual ward model delivers clinical care remotely to patients in isolation. We report on an Australian cohort of patients with COVID-19 treated in a virtual ward. OBJECTIVE: The aim of this study was to describe and evaluate the safety and efficacy of a virtual ward model of care for an Australian cohort of patients with COVID-19. METHODS: Retrospective clinical assessment was performed for 223 patients with confirmed COVID-19 treated in a virtual ward in Brisbane, Australia, from March 25 to May 15, 2020. Statistical analysis was performed for variables associated with the length of stay and hospitalization. RESULTS: Of 223 patients, 205 (92%) recovered without the need for escalation to hospital care. The median length of stay in the virtual ward was 8 days (range 1-44 days). In total, 18 (8%) patients were referred to hospital, of which 6 (33.3%) were discharged after assessment at the emergency department. Furthermore, 12 (5.4%) patients were admitted to hospital, of which 4 (33.3%) required supplemental oxygen and 2 (16.7%) required mechanical ventilation. No deaths were recorded. Factors associated with escalation to hospital care were the following: hypertension (odds ratio [OR] 3.6, 95% CI 1.28-9.87; P=.01), sputum production (OR 5.2, 95% CI 1.74-15.49; P=.001), and arthralgia (OR 3.8, 95% CI 1.21-11.71; P=.02) at illness onset and a polymerase chain reaction cycle threshold of ≤20 on a diagnostic nasopharyngeal swab (OR 5.0, 95% CI 1.25-19.63; P=.02). CONCLUSIONS: Our results suggest that a virtual ward model of care to treat patients with COVID-19 is safe and efficacious, and only a small number of patients would potentially require escalation to hospital care. Further studies are required to validate this model of care.

Diagnostic approach to chronic dyspnoea in adults.

Chronic dyspnoea, or breathlessness for more than four weeks duration, is a common symptom in adults presenting to primary and tertiary care. It often presents a diagnostic challenge due to the wide spectrum of underlying disease, which is multifactorial in approximately one third of cases. Challenges in diagnosis include an often non-diagnostic clinical assessment, difficulty in selecting the most appropriate investigations and correct speciality referral for further diagnostic assessment. In patients presenting with chronic dyspnoea, history and physical examination are often non-specific with key findings more useful as negative predictive factors. There is a broad range of simple to specialised investigations that may be utilised in the diagnostic workup. Several diagnostic algorithms incorporating different tiers of investigations have been tested in studies of chronic dyspnoea patients but there is currently very limited data that test a diagnostic algorithm against standard clinical care. In this review we propose a diagnostic pathway with primary, secondary and tertiary level investigations for patients with chronic dyspnoea. This pathway is based on the combination of previously tested diagnostic algorithms in the literature, to assist clinicians in their diagnostic workup of chronic dyspnoea patients. Further research is needed to further evaluate diagnostic algorithms in this setting and to test this diagnostic pathway in clinical practice.

Clinical management practices of life-threatening asthma: an audit of practices in intensive care.

OBJECTIVE: Lack of management guidelines for lifethreatening asthma (LTA) risks practice variation. This study aims to elucidate management practices of LTA in the intensive care unit (ICU). DESIGN: A retrospective cohort study. SETTING: Thirteen participating ICUs in Australia between July 2010 and June 2013. PARTICIPANTS: Patients with the principal diagnosis of LTA. MAIN OUTCOME MEASURES: Clinical history, ICU management, patient outcomes, ward education and discharge plans. RESULTS: Of the 270 (267 patients) ICU admissions, 69% were female, with a median age of 39 years (interquartile range [IQR], 26-53 years); 119 (44%) were current smokers; 89 patients (33%) previously required ICU admission, of whom 23 (25%) were intubated. The median ICU stay was 2 days (IQR, 2-4 days). Three patients (1%) died. Seventy-nine patients (29%) received non-invasive ventilation, with 11 (14%) needing subsequent invasive ventilation. Sixty-eight patients (25%) were intubated, with the majority of patients receiving volume cycled synchronised intermittent mechanical ventilation (n = 63; 93%). Drugs used included ß2-agonist by intravenous infusion (n = 69; 26%), inhaled adrenaline (n = 15; 6%) or an adrenaline intravenous infusion (n = 23; 9%), inhaled anticholinergics (n = 238; 90%), systemic corticosteroids (n = 232; 88%), antibiotics (n = 126; 48%) and antivirals (n = 22; 8%). When suitable, 105 patients (n = 200; 53%) had an asthma management plan and 122 (n = 202; 60%) had asthma education upon hospital discharge. Myopathy was associated with hyperglycaemia requiring treatment (odds ratio [OR], 31.6; 95% CI, 2.1-474). Asthma education was more common under specialist thoracic medicine care (OR, 3.0; 95% CI, 1.61-5.54). CONCLUSION: In LTA, practice variation is common, with opportunities to improve discharge management plans and asthma education.

Diagnosis of the cause of chronic dyspnoea in primary and tertiary care: characterizing diagnostic confidence.

BACKGROUND: Chronic dyspnoea (breathlessness) in adults is a common symptom, the exact cause of which may be difficult to diagnose on initial presentation. We characterised the diagnostic complexity of chronic dyspnoea in primary care and tertiary care. METHODS: This retrospective observational study screened consecutive referral letters of all adult patients referred to cardiology or respiratory clinics at a tertiary referral hospital, during May to June 2015. For patients referred due to chronic dyspnoea, data were analysed from the initial referral letter and subsequent specialist clinic letters for the 6-month time period after referral. RESULTS: Of 1,370 patient referrals, 122 patients (mean age 63 y, 55% female) were referred due to chronic dyspnoea. One hundred and five patients (86%) were referred from primary care and 17 (14%) from other hospital clinics. Sixty-one percent were referred with an evident diagnosis (referrer was confident of the initial diagnosis), whereas 39% had non-evident or unclear diagnoses. By 6 months after referral, a definitive final diagnosis had been determined by the specialist clinics in 62% of patients. The majority of patients had been referred appropriately to a cardiology or respiratory clinic, based on the final diagnosis. However, only 26% of diagnoses were fully concordant between the initial referrer diagnosis and the final specialist clinic diagnosis, with 26% being partially concordant and 48% non-concordant. Diagnostic certainty of the referrer was associated with concordance of diagnosis between the referrer and specialist clinic (P<0.001). CONCLUSIONS: In adult patients referred due to chronic dyspnoea to hospital specialist clinics, there is considerable diagnostic uncertainty about its aetiology, for both referring doctors and specialist clinics. These results demonstrate the current difficulty in diagnosing the cause of chronic dyspnoea in adults, and highlight the need for evidence-based diagnostic pathways.

Early life environmental predictors of asthma age-of-onset.

Prevention strategies that delay the onset of asthma may improve clinical outcomes. To identify early life environmental exposures associated with asthma age-of-onset and potential genetic modifiers of these exposures, we studied 1085 subjects with physician-diagnosed asthma and disease onset at or after age two. Subjects reported retrospectively on their exposure to 17 environmental factors before the age of two. The presence of individual or combinations of these early life exposures was then tested for association with variation in asthma age-of-onset. For exposures significantly associated with age-of-onset, we tested if 26 single nucleotide polymorphisms (SNP) with an established association with allergic disease significantly modified the effect of the exposure. Five environmental exposures were significantly associated with variation in asthma age-of-onset after correction for multiple testing: carpet at home (P = 6 × 10(-5)), a serious chest illness (P = 10(-4)), father a cigarette smoker (P = 6 × 10(-4)) and direct exposure to father's smoking (P = 3 × 10(-4)). Individuals with early childhood asthma onset, between the ages of two and six, were 1.4-fold (CI 1.1-1.9) more likely to report having lived in a house with carpet and 2.1-fold (CI 1.3-3.5) more likely to report suffering a serious chest illness before the age of two, than asthmatics with later disease onset. We further found these individual risks to increase to 3.2-fold (CI 1.7-6.0) if carpet exposure and suffering a serious chest illness co-occurred before age two. Paternal smoking exposures were less likely to be reported by asthmatics with early when compared to later disease onset (OR 0.5, CI 0.3-0.7). There were no significant SNP interactions with these environmental exposures after correction for multiple testing. Our results suggest that disease onset in individuals at a high-risk of developing asthma can potentially be delayed by avoiding exposure to carpet at home and preventing serious chest illnesses during the first 2 years of life.