Think twice - Diagnostic delay in a patient with acute chest pain

AbstractHeart involvement is the most critical and potentially lethal systemic manifestation in eosinophilic granulomatosis with polyangiitis (EGPA).We present a case of acute chest pain in a 58-year-old male with severe asthma, which regressed after sublingual administration of nitroglycerine. At the time of hospital admission, there were non-specific ST-changes on the ecg, coronary enzymes were increased, and the patient was concluded to have a non-ST-elevation myocardial infarction, and treated as such.A subacute cardiac catheterization showed no signs of significant coronary stenosis. During the next days, there was increasing pain and reduced strength in both feet. Paraclinical imaging and neurological examinations could not explain the symptoms, and physiotherapy was initiated. At the time, no connection to patient's diagnosis of severe asthma was made.The patient was seen in the respiratory outpatient clinic for a routine check-up, three weeks after the initial hospital admission. At this point, there was increasing pain in both legs and the patient had difficulty walking and experienced increasing dyspnea. Blood eosinophils were elevated (12.7 × 109/L), and an acute HRCT scan showed bilateral peribronchial infiltrates with ground glass opacification and small noduli.A diagnosis of EGPA was established, and administration of systemic glucocorticoids was initiated. A year and a half later, there is still reduced strength and sensory loss.This case illustrates that it is important to consider alternative diagnoses in patients with atypical symptoms and a low risk profile.Heart involvement is the most critical and potentially lethal systemic manifestation in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), which makes a quick diagnosis and prompt initiation of correct treatment imperative

Diagnostic work-up in patients with possible asthma referred to a university hospital

OBJECTIVE: The best strategy for diagnosing asthma remains unclear. Accordingly, the aim of this study was to evaluate diagnostic strategies in individuals with possible asthma referred to a respiratory outpatient clinic at a university hospital. METHODS: All individuals with symptoms suggestive of asthma referred over 12 months underwent spirometry, bronchodilator reversibility test, Peak expiratory flow rate (PEF) registration, and bronchial challenge test with methacholine and mannitol on three separate days. The results of these tests were compared against an asthma diagnosis based on symptoms, presence of atopy and baseline spirometry made by a panel of three independent respiratory specialists. RESULTS: Of the 190 individuals examined, 63% (n=122) were classified as having asthma. Reversibility to β(2)-agonist had the lowest sensitivity of 13%, whereas airway hyperresponsiveness to methacholine had the highest (69%). In contrast, specificity was the highest for reversibility testing (93%), whereas methacholine had the lowest specificity (57%). The combination of reversibility, peak-flow variability, and methacholine yielded a cumulative sensitivity of 78%, albeit a specificity of 41%. In comparison, a combination of reversibility and mannitol resulted in a specificity of 82% and a sensitivity of 42%. CONCLUSION: In this real-life population, different diagnostic test combinations were required to achieve a high specificity for diagnosing asthma and a high sensitivity, respectively: Our findings suggest that the diagnostic test approach should be based on whether the aim is to exclude asthma (high sensitivity required) or confirm a diagnosis of asthma (high specificity required)

Real-world, long-term effectiveness of allergy immunotherapy in allergic rhinitis: Subgroup analyses of the REACT study

Background: Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet. // Objective: We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet. // Methods: The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects. // Results: Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite–specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets. // Conclusions: These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR

Imiquimod shows anti-viral actions in human bronchial epithelium - implications for COVID-19 treatment

Introduction: Combining anti-viral and anti-inflammatory effects in a single drug may be beneficial in treating COVID-19. We hypothesized that the TLR7 agonist imiquimod (imq) may exert these actions in human bronchial epithelial cells (HBECs), which are targets in SARS-CoV-2 mediated lung injury. Methods: Using primary HBECs from asthmatic donors (N=18), we explored actions of imq related to airway viral resistance and tolerance. HBECs were treated with imq alone or in combination with the viral mimic poly (I:C) or the SARS-CoV-2 spike protein 1 (SP1). Anti-viral and pro-inflammatory mediators were analyzed by Luminex, RT-qPCR and mRNA gene pathway analysis. Results: imq treatment alone induced IFN-ß and CCL5 (p<0.05) mRNA and reduced transcription of IL-1ß (p<0.01) at 24h. In SP1 or poly (I:C) stimulated HBECs, treatment with imq augmented IFN-ß mRNA expression by a 2-fold, respectively (p<0.05). Imq in combination with poly (I:C) decreased protein release of IL-8, CCL5, IL-1ß and IL-6 (p<0.05). Furthermore, gene pathway analysis revealed that imq enriched poly(I:C)-induced IFN signaling, IL-20 family signaling (epithelial repair), antigen presentation and cytokine signaling. Enriched cytokine signaling genes included negative regulators such as IKBKG and SIGIRR. Conclusion: imq exerts distinct anti-viral resistance effects in HBECs by increasing anti-viral signaling and improves viral infection tolerance by diminishing epithelial cytokines potentially involved in severe COVID-19. Our findings highlight a possibility of developing dual action drugs suitable for anti-SARS-CoV-2 treatment

High baseline prevalence of atopic comorbidities and medication use in children treated with allergy immunotherapy in the REAl-world effeCtiveness in allergy immunoTherapy (REACT) study

BackgroundRespiratory allergy, commonly manifesting as allergic rhinitis (AR) and asthma, is a chronic progressive disease that frequently starts in childhood. Allergy immunotherapy (AIT) is the only causal treatment for respiratory allergy with the potential to modify the underlying cause of allergy and, ultimately, prevent disease progression. This analysis aimed to determine if AIT is received sufficiently early to halt the progression of allergic disease, by characterizing the burden and progression of disease in children prior to AIT initiation in real-life clinical practice.MethodsThe REAl-world effeCtiveness in allergy immunoTherapy (REACT) study was a large retrospective cohort study using German claims data between 2007 and 2017. Characteristics of two pre-defined AIT age cohorts from the REACT study – children (aged &lt;18 years) and adults (aged ≥18 years) – were evaluated during the 1-year period before the first AIT prescription. For comparison, a control group of all subjects with a confirmed diagnosis of AR and without prescriptions for AIT was included. Burden of disease was assessed using diagnostic codes for atopic comorbidities [e.g., atopic dermatitis (AD), asthma, and acute allergic conjunctivitis] and non-atopic comorbidities (e.g., migraine, headache); medication use, recorded as prescriptions for symptom-relieving AR medication and reliever/controller medication for asthma, was also assessed. Data were analyzed descriptively, using summary statistics.ResultsBoth children (n = 11,036) and adults (n = 30,037) showed a higher prevalence of atopic comorbidities and a greater drug burden prior to AIT initiation compared to AR patients not treated with AIT (n = 1,003,332). In the two age-specific AIT cohorts, children consistently showed the highest prevalence of atopic comorbidities compared to adults (AIT children, AIT adults – asthma: 41.4%, 34.5%; AD: 19.9%, 10.2%; acute allergic conjunctivitis: 13.6%, 10.2%). Generally, prescriptions per year for symptom-relieving AR and asthma treatments were also higher for children initiating AIT vs. adults (AIT children, AIT adults – AR prescriptions per subject: 1.72, 0.73; asthma prescriptions per subject: 1.42, 0.79).ConclusionsChildren with AR who are offered AIT in real-life show considerable disease burden prior to initiation. As AIT may alleviate the burden and halt the progression of allergic disease, considering AIT earlier in the disease course may be warranted

Breathing Exercises for Patients with Asthma in Specialist Care:A Multicenter Randomized Clinical Trial

RATIONALE: Moderate to severe asthma is associated with impaired asthma control and quality of life (QoL) despite access to specialist care and modern pharmacotherapy. Breathing exercises (BrEX) improve QoL in incompletely controlled mild asthma, but impact in moderate to severe asthma is unknown. OBJECTIVES: To investigate the effectiveness of BrEX as adjuvant treatment on QoL in patients with uncontrolled moderate to severe asthma. METHODS: Adult patients with incompletely controlled asthma attending respiratory specialist clinics were randomized to usual specialist care (UC) or UC and BrEX (UC + BrEX) with three individual physiotherapist-delivered sessions and home exercises. Primary outcome was asthma-related QoL (Mini-Asthma Quality of Life Questionnaire [Mini-AQLQ]) at 6 months on the basis of intention-to-treat analysis. Secondary outcomes: Mini-AQLQ at 12 months, lung function, 6-minute-walk test, physical activity level, Nijmegen Questionnaire, Hospital Anxiety and Depression Scale, and adverse events. Repeated-measures mixed-effects models were used to analyze data. Poisson regression models were used to analyze adverse event incidence rate ratio. RESULTS: A total of 193 participants were allocated to UC + BrEX (n = 94) or UC (n = 99). UC + BrEX was superior in the primary outcome (adjusted mean change difference, 0.35; 95% confidence interval [CI], 0.07 to 0.62). Superiority in Mini-AQLQ was sustained at 12 months (0.38; 95% CI, 0.12 to 0.65). A minor improvement in Hospital Anxiety and Depression Scale depression score at 6 months favoring UC + BrEX (−0.90; 95% CI, −1.67 to −0.14) was observed. Asthma-related adverse events occurred similarly in UC + BrEX and UC participants: 14.9% versus 18.1% (P = 0.38). CONCLUSIONS: BrEX as add-on to usual care improve asthma-related QoL in incompletely controlled asthma regardless of severity and with no evidence of harm. Clinical trial registered with www.clinicaltrials.gov (NCT 03127059)

Complete response to anti-interleukin-5 biologics in a real-life setting:results from the nationwide Danish Severe Asthma Register

BACKGROUND: Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma. METHODS: This prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS. RESULTS: A total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ −1.04 versus −0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils. CONCLUSIONS: More than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders

What bothers severe asthma patients most? A paired patient-clinician study across seven European countries

Introduction: Severe asthma is a complex, multi-dimensional disease. Optimal treatment adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries. Methods: Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most bothersome aspect(s) of their asthma. Patients’ responses were linked with their treating clinician who also completed free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients. Results: Eighty-eight codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on ‘holistic’ aspects such as the effort required to self-manage their disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low in younger patients and those infrequently using oral corticosteroids. In asthma registries, patient aspects were predominantly represented in questionnaires. Conclusions: Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multi-disciplinary treatment teams. The use of questionnaires that include multi-faceted aspects of disease may result in improved asthma research