IL-17 Aggravates Pseudomonas aeruginosa Airway Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Pseudomonas aeruginosa airway infection increases risks of exacerbations and mortality in chronic obstructive pulmonary disease (COPD). We aimed to elucidate the role of IL-17 in the pathogenesis. We examined the expression and influences of IL-23/IL-17A in patients with stable COPD (n = 33) or acute COPD exacerbations with P. aeruginosa infection (n = 34). A mouse model of COPD (C57BL/6) was used to investigate the role of IL-17A in host inflammatory responses against P. aeruginosa infection through the application of IL-17A–neutralizing antibody or recombinant IL-17A. We found that P. aeruginosa infection increased IL-23/17A signaling in lungs of both COPD patients and COPD mouse models. When COPD mouse models were treated with neutralizing antibody targeting IL-17A, P. aeruginosa induced a significantly less polymorphonuclear leukocyte infiltration and less bacterial burden in their lungs compared to those of untreated counterparts. The lung function was also improved by neutralizing antibody. Furthermore, IL-17A-signaling blockade significantly reduced the expression of pro-inflammatory cytokine IL-1β, IL-18, TNF-α, CXCL1, CXCL15 and MMP-9, and increased the expression of anti-inflammatory cytokine IL-10 and IL-1Ra. The application of mouse recombinant IL-17A exacerbated P. aeruginosa-mediated inflammatory responses and pulmonary dysfunction in COPD mouse models. A cytokine protein array revealed that the expression of retinol binding protein 4 (RBP4) was down-regulated by IL-17A, and exogenous RBP4-recombinant protein resulted in a decrease in the severity of P. aeruginosa-induced airway dysfunction. Concurrent application of IL-17A-neutralizing antibody and ciprofloxacin attenuated airway inflammation and ventilation after inoculation of P. aeruginosa in COPD mouse models. Our results revealed that IL-17 plays a detrimental role in the pathogenesis of P. aeruginosa airway infection during acute exacerbations of COPD. Targeting IL-17A is a potential therapeutic strategy in controlling the outcomes of P. aeruginosa infection in COPD patients.

Flare management in atopic dermatitis: from definition to treatment

Atopic dermatitis (AD) is a skin immune-mediated inflammatory disease with a chronic-recurrent course. Acute exacerbations or flares are an integral part of the AD course and are generally defined as disease worsening, requiring escalation/intensification of treatment. Management of flares is crucial since their prevention is a key aim of long-term disease control. Nevertheless, difficulties related to this aspect are several, starting from the definition of flare itself, which is not always satisfactory or unambiguous, and needs clarification. Indeed, this hurdle may reduce clarity on treatment choice and generate difficulties when comparing data between studies. Deepening our knowledge on flares could be highly relevant to both clinicians and patients to provide adequate control of the disease through patient education and appropriate treatment. This review aims to summarize current knowledge on the management of AD flares from definition to treatment, highlighting aspects that are still unclear, and identifying any necessary unmet needs to better manage AD.

A Systematic Review and Meta-Analysis of the Prevalence and Impact of Pulmonary Bacterial Colonisation in Stable State Chronic Obstructive Pulmonary Disease (COPD)

Background: Half of acute exacerbations of COPD are due to bacterial infection, and the other half are likely influenced by microbial colonisation. The same organisms commonly cultured during acute exacerbations are often found in the sputum of patients during stability. A robust assessment of the prevalence of potentially pathogenic microorganisms (PPMs) in the sputum of stable COPD patients may help to inform the targeted prevention of exacerbation by these organisms. Methods: A systematic review and meta-analysis was carried out to determine the prevalence of PPMs in patients with COPD in the stable state. Meta-analysis of prevalence was carried out using the Freeman–Tukey double arcsine transformation random effects model, and sub-group analysis was performed for sputum modality. Prevalence of total and individual PPMs was calculated from patient-level data from individual studies. Results: Pooled prevalence of PPMs identified by sputum culture was found to be 41% (95% CI 36–47%). Significant heterogeneity was found across all studies, which can likely be attributed to inconsistent measuring and reporting of PPMs. The most commonly reported organisms were H. influenzae, M catarrhalis, S. pneumoniae, S. aureus, and P. aeruginosa. Declining lung function was weakly correlated with prevalence of PPMs. Conclusion: The airways of patients with COPD are colonised with PPMs during the stable state in almost half of patients. A complex relationship likely exists between the microbiome in the stable state and the phenotype of COPD patients. Targeted microbial therapy for preventing exacerbations of COPD should carefully consider the stable microbiome as well as the exacerbated.

Physical Tests Are Poorly Related to Patient-Reported Outcome Measures during Severe Acute Exacerbations of COPD

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a negative impact on patients’ health status, including physical function and patient-reported outcomes. We aimed to explore the associations between physical tests and patient-reported outcome measures (PROMs) in hospitalised patients for an AECOPD. Patients were assessed on the day of discharge. Quadriceps force, handgrip strength, short physical performance battery (SPPB), five-repetition sit-to-stand test (5STS), four-meter gait speed test (4MGS), balance test, six-minute walk test (6MWT), COPD Assessment Test (CAT), London Chest Activity of Daily Living scale (LCADL), modified Medical Research Council (mMRC) dyspnea scale, Checklist of Individual Strength (CIS)-fatigue subscale, and Patient Health Questionnaire (PHQ-9) were collected. Sixty-nine patients with an AECOPD were included (54% female; age 69 ± 9 years; FEV1 39.2 (28.6–49.1%) predicted). Six-minute walk distance was strongly correlated with mMRC (ρ: −0.64, p < 0.0001) and moderately correlated with LCADL total score, subscales self-care and household activities (ρ ranging from −0.40 to −0.58, p < 0.01). Moreover, 4MGS was moderately correlated with mMRC (ρ: −0.49, p < 0.0001). Other correlations were weak or non-significant. During a severe AECOPD, physical tests are generally poorly related to PROMs. Therefore, a comprehensive assessment combining both physical tests and PROMs needs to be conducted in these patients to understand their health status.

Lung Ultrasound in Pediatric Asthma - Characterizing Baseline Findings Outside of Acute Exacerbations

Background: Lung ultrasound (LUS) has been shown to be an effective tool to rapidly diagnose certain causes of pediatric respiratory distress in the emergency department. However, very little is known about LUS findings in pediatric asthma outside of acute exacerbations. Objectives: The primary objective of this study was to characterize LUS findings in a cohort of pediatric patients with a definitive diagnosis of asthma, outside of an asthma exacerbation. Methods: Eligible patients, aged 6 to 17 years old and diagnosed with asthma, underwent LUS during an outpatient visit. LUS was conducted using a six-zone scanning protocol. A positive LUS was defined by one or more of the following: ≥3 B-lines per intercostal space, pulmonary consolidation and/or pleural anomaly. Images were interpreted by an expert sonographer blinded to patient clinical characteristics. Results: 52 patients were included. 10/52 patients had a positive LUS (19.2%, 95CI 8.3-30.1%). Of those with positive LUS findings, 8 had B lines, 7 had consolidations <1cm, 1 had a pleural line abnormality and 1 had a consolidation >1cm. Positive findings were seen in the right anterior and lateral zones in 60% of participants and were limited to 1-2 intercostal spaces within one lung zone in 100% of participants. Conclusion: To our knowledge, this is the first report of LUS findings in outpatient pediatric asthma. Positive LUS findings in asthmatic children can be seen outside of acute exacerbations. Such findings need to be taken into consideration when using LUS for the acute evaluation of a pediatric patient with asthma.

Acute asthma

Asthma is a common chronic condition, characterised by episodic acute exacerbations, which may require emergency treatment. According to Asthma UK, nationally 5 400 000 people are being treated for asthma; with life-threatening asthma attacks occurring every 10 seconds and three lives lost daily. In acute asthma, symptoms, including breathlessness, chest tightness, wheeze and cough, deteriorate progressively. Individuals with asthma symptoms often present to primary care and it is important that GPs can recognise and appropriately manage acute asthma. This article reviews the background, recognition and management of acute asthma in adults and children over the age of five, drawing on current guidelines.

RACer-PAP. Investigating the utility and acceptability of a new non-invasive ventilatory assist device, during exercise, in a population of normal, healthy adults: A feasibility study. (Preprint)

BACKGROUND Non-Invasive Ventilation (NIV) has been demonstrated to benefit people who have moderate to severe COPD during acute exacerbations. Studies have begun to investigate the effectiveness of NIV during pulmonary rehabilitation (PR) to improve outcomes for people with COPD, however the lack of portability and humidification of these devices means the use of such devices is limited, especially when performing activities of daily living. A new prototype device, RACer-PAP, delivers battery-operated positive airway pressure via a nasal interface whilst regulating nasal airway apportionment bias, removing the need for supplementary humidification. This device may offer people with COPD an improved ability to participate in PR and activities of daily living. OBJECTIVE To assess the feasibility of exercising with the RACer-PAP in situ and the acceptability of the device during exercise in normal, healthy individuals. METHODS 15 healthy adults were invited to attend two exercise sessions, one week apart, to assess baseline 6-minute walk distance (6MWD) with and without the RACer-PAP in situ. Vital signs and spirometry were monitored throughout, and spirometry was taken pre and post RACer-PAP testing. Subjective questionnaires ascertained participant feedback on exercising with the device in situ. RESULTS 14 (93%) participants completed both sessions. There were no adverse events associated with exercising with the device in situ. There were no differences in vital signs and 6MWD whether exercising with or without the device in situ. There were small increases in maximum dyspnoea scores (on Borg scale) on exercise with the device in situ compared with no device on exercise (median/IQR: 2.0/0.5-3.0 vs 3.0/2.0-3.25). There were small increases in forced vital capacity following exercise with the RACer-PAP. None of the participants reported symptoms associated with airway drying. Participant feedback provided recommendations for modifications for the next iteration of the device, prior to piloting the device with people with COPD. CONCLUSIONS This study has shown RACer-PAP to be safe and feasible to use during exercise and has provided feedback for modifications to the device to improve its use during exercise. We now propose to consider the application of the device in a small pilot feasibility study to assess safety, feasibility and utility of the device in a population of people with moderate to severe COPD. CLINICALTRIAL The study was prospectively registered and approved on ACTRN12619000478112 on 22/03/2019.

A multifaceted stewardship intervention helps curb steroid overprescribing in hospitalized patients with acute exacerbations of COPD

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Corticosteroid overprescribing is well documented in real-world practice. There is currently no evidence to guide best practices for steroid stewardship. The aim of this study was to assess the effects of a 3-part stewardship intervention strategy on inpatient steroid prescribing in patients with acute exacerbations of COPD (AECOPD). Summary Investigators implemented a 3-part stewardship initiative consisting of (1) an anonymous survey for providers on steroid prescribing in a simplified case of AECOPD, (2) face-to-face education and review of survey results, and (3) prospective audit and feedback from a clinical pharmacist. This was a quasi-experimental before-and-after study evaluating hospitalized adults diagnosed with AECOPD in two 12-month study periods before (April 2019-March 2020) and after (May 2020-April 2021) implementation. The primary outcome was mean inpatient steroid dosing. Secondary outcomes were duration of therapy, length of stay (LOS), 30-day readmissions, 30-day mortality, and incidence of hyperglycemia. Per power analysis, there were 27 patients per cohort. The interventions resulted in a significant reduction in prednisone equivalents during hospitalization: 118 mg vs 53 mg (P = 0.0003). This decrease was similar in ICU (160 mg vs 61 mg, P = 0.008) and non-ICU (102 mg vs 49 mg, P = 0.004) locations. There was no significant difference in duration of therapy (8 days vs 7 days, P = 0.44), length of stay (3.3 days vs 3.9 days, P = 0.21), 30-day mortality (4% vs 7%, P = 0.55), 30-day readmissions (15% vs 7%, P = 0.39), or rate of hyperglycemia (48% vs 44%, P = 0.78). Conclusion A multifaceted stewardship intervention significantly reduced steroid dosing in hospitalized AECOPD patients. This reduction was not associated with known deleterious effects.