23 February 2022


Phillips TM, Moloney C, Sneath E, Beccaria G, Issac H, Mullens AB, Gow J, Rana R, King A. Associated factors, assessment, management, and outcomes of patients who present to the emergency department for acute exacerbation of chronic obstructive pulmonary disease: A scoping review. Respir Med. 2022 Jan 21;193:106747. doi: 10.1016/j.rmed.2022.106747. Epub ahead of print. PMID: 35086024.
Objective: The purpose of the scoping review was to examine the extant literature for factors contributing to presentations of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) to Emergency Departments (ED).
Methods: The review followed Arksey and O’Malley, and Levac’s frameworks supplemented with the PRISMA-ScR checklist. We searched Cochrane Library, CINAHL, JBI, and PubMed from January 1, 2008 to March 23, 2020 for inclusions. We included studies reporting ED presentations for AECOPD among adults (≥18 years). The investigation included: pre-hospital factors; ED-related assessment, management and referral practices; holistic management (i.e., interdisciplinary); patient outcomes, admission/discharge status, and readmission.
Results: Forty-four studies were included. Environmental factors (e.g., air pollution, seasonal change); social determinants (e.g., poor literacy, ethnicity); and physical health (e.g., comorbidities, obesity, poor exercise capacity) contributed to ED presentation/re-presentation, and admission to hospital. Cigarette smoking was associated with hospital admission. Mortality was associated with longer-term oxygen therapy, poor exercise capacity, age, and loss of consciousness. Compliance with clinical guideline recommendations were generally low or mixed. Further, there was a lack of appropriate referral practices upon discharge.
Conclusions: While there is considerable literature on factors contributing to AECOPD admission more research is required that investigates the impact that inter-professional care models can have on the discharge planning cycles for patients with COPD who are regular presenters to an ED.

Sheikh S, Hamilton FW, Nava GW, Gregson FKA, Arnold DT, Riley C, Brown J; AERATOR Group, Reid JP, Bzdek BR, Maskell NA, Dodd JW. Are aerosols generated during lung function testing in patients and healthy volunteers? Results from the AERATOR study. Thorax. 2022 Mar;77(3):292-294. doi: 10.1136/thoraxjnl-2021-217671. Epub 2021 Nov 2. PMID: 34728573.
Pulmonary function tests are fundamental to the diagnosis and monitoring of respiratory diseases. There is uncertainty around whether potentially infectious aerosols are produced during testing and there are limited data on mitigation strategies to reduce risk to staff. Healthy volunteers and patients with lung disease underwent standardised spirometry, peak flow and FENO assessments. Aerosol number concentration was sampled using an aerodynamic particle sizer and an optical particle sizer. Measured aerosol concentrations were compared with breathing, speaking and voluntary coughing. Mitigation strategies included a standard viral filter and a full-face mask normally used for exercise testing (to mitigate induced coughing). 147 measures were collected from 33 healthy volunteers and 10 patients with lung disease. The aerosol number concentration was highest in coughs (1.45-1.61 particles/cm3), followed by unfiltered peak flow (0.37-0.76 particles/cm3). Addition of a viral filter to peak flow reduced aerosol emission by a factor of 10 without affecting the results. On average, coughs produced 22 times more aerosols than standard spirometry (with filter) in patients and 56 times more aerosols in healthy volunteers. FENO measurement produced negligible aerosols. Cardiopulmonary exercise test (CPET) masks reduced aerosol emission when breathing, speaking and coughing significantly. Lung function testing produces less aerosols than voluntary coughing. CPET masks may be used to reduce aerosol emission from induced coughing. Standard viral filters are sufficiently effective to allow guidelines to remove lung function testing from the list of aerosol-generating procedures
Important message: lung function testing with filters not generating aerosol i.e. are safe

Kulbacka-Ortiz K, Triest FJJ, Franssen FME, Wouters EFM, Studnicka M, Vollmer WM, Lamprecht B, Burney PGJ, Amaral AFS, Vanfleteren LEGW. Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study. Respir Res. 2022 Feb 17;23(1):34. doi: 10.1186/s12931-022-01939-5. PMID: 35177082.

O’Driscoll JM, Giannoglou D, Bashar I, Kipourou K, Alati E, Madden B, Marciniak A, Sharma R. Undiagnosed Chronic Obstructive Pulmonary Disease is Highly Prevalent in Patients Referred for Dobutamine Stress Echocardiography with Shortness of Breath. Lung. 2022 Feb 15. doi: 10.1007/s00408-022-00512-7. Epub ahead of print. PMID: 35166905.
Purpose: Shortness of breath (SOB) is a common symptom referral for dobutamine stress echocardiography (DSE). Patients with SOB and a normal DSE have worse long-term outcome than the general population. This suggests multiple aetiologies are involved. The purpose of this study was to assess the prevalence and clinical significance of undiagnosed COPD amongst patients referred for a DSE with SOB.
Methods: We prospectively studied 114 patients referred for DSE with SOB without prior evidence of lung disease (mean age 64.9 ± 18.5 years, 60 male). Respiratory function testing using spirometry was performed on all patients on the day of their DSE. The study end-points were cardiac events and total mortality.
Results: Respiratory function testing and DSE was performed in all patients and COPD was highly prevalent (n = 93). Multivariate Cox regression analysis was used to estimate the effect of dyspnoea on non-fatal cardiac events (NFCE) and all-cause mortality. Over a mean follow-up of 4.5 ± 2.6 years, the composite end-point of NFCE and all-cause mortality occurred in 62.7% and 16.7% patients, respectively. COPD (HR 1.27; 95% CI 1.17-1.93), previous myocardial infarction (HR 1.84; 95% CI 1.06-3.2), myocardial ischaemia (HR 2.56; 95% CI 1.48-4.43), peak wall motion score index (HR 4.66; 95% CI 2.26-9.6), and mitral E/E’ (HR 1.21; 95% CI 1.1-1.33) were significantly associated with a NFCE. Myocardial ischaemia (HR 4.43; 95% CI 1.24-15.81) was the only independent predictor of all-cause mortality.
Conclusion: Undiagnosed COPD is highly prevalent and independently associated with worse outcome amongst patients with SOB referred for DSE. Symptom presentation is therefore an important consideration when interpreting DSE result

Singh D, Wild JM, Saralaya D, Lawson R, Marshall H, Goldin J, Brown MS, Kostikas K, Belmore K, Fogel R, Patalano F, Drollmann A, Machineni S, Jones I, Yates D, Tillmann HC. Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial. Respir Res. 2022 Feb 10;23(1):26. doi: 10.1186/s12931-022-01949-3. PMID: 35144620; PMCID: PMC8832861.

Vikjord SAA, Brumpton BM, Mai XM, Romundstad S, Langhammer A, Vanfleteren L. The HUNT study: Association of comorbidity clusters with long-term survival and incidence of exacerbation in a population-based Norwegian COPD cohort. Respirology. 2022 Feb 10. doi: 10.1111/resp.14222. Epub ahead of print. PMID: 35144315.
Background and objective: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease often viewed as part of a multimorbidity complex. There is a need for better phenotyping of the disease, characterization of its interplay with other comorbidities and its association with long-term outcomes. This study aims to examine how clusters of comorbidities are associated with severe exacerbations and mortality in COPD.
Methods: Participants with potential COPD were recruited from the second (1995-1997) and third (2006-2008) survey of the HUNT Study and followed up until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe COPD exacerbations requiring hospitalization were assessed using hospital data. All-cause mortality was collected from national registries. Multivariable Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between comorbidity clusters and all-cause mortality. Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for the cumulative number of severe exacerbations for each cluster.
Results: Five distinct clusters were identified, including ‘less comorbidity’, ‘psychological’, ‘cardiovascular’, ‘metabolic’ and ‘cachectic’ clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality (HR 1.23 [1.04-1.45] and HR 1.83 [1.52-2.20], adjusted for age and sex). The same clusters also had increased risk of exacerbations (unadjusted IRR of 1.24 [95% CI 1.04-1.48] and 1.50 [95% CI 1.23-1.83], respectively).
Conclusion: During 25 years of follow-up, individuals in the psychological and cachectic clusters had increased mortality. Furthermore, these clusters were associated with increased risk of severe COPD exacerbations.
Keywords: COPD exacerbation; HUNT study; chronic obstructive pulmonary disease; clinical epidemiology; comorbidity cluster.

Pando-Sandoval A, Ruano-Ravina A, Candal-Pedreira C, Rodríguez-García C, Represas-Represas C, Golpe R, Fernández-Villar A, Pérez-Ríos M. Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review. Clin Respir J. 2022 Feb 10. doi: 10.1111/crj.13479. Epub ahead of print. PMID: 35142054.

Putcha N, Woo H, McCormack MC, Fawzy A, Romero K, Davis MF, Wise RA, Diette GB, Koehler K, Matsui EC, Hansel NN. Home Dust Allergen Exposure Is Associated with Outcomes among Sensitized Individuals with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2022 Feb 15;205(4):412-420. doi: 10.1164/rccm.202103-0583OC. PMID: 34752729.
Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (β, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George’s Respiratory Questionnaire Total Score (β, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD

Mkorombindo T, Balmes JR, Custovic A, Dransfield MT. The Air We Breathe: Respiratory Impact of Indoor Air Quality in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2022 Feb 15;205(4):378-380. doi: 10.1164/rccm.202112-2822ED. PMID: 35007496.


Louis R, Satia I, Ojanguren I, Schleich F, Bonini M, Tonia T, Rigau D, Ten Brinke A, Buhl R, Loukides S, Kocks JWH, Boulet LP, Bourdin A, Coleman C, Needham K, Thomas M, Idzko M, Papi A, Porsbjerg C, Schuermans D, Soriano JB, Usmani OS. European Respiratory Society Guidelines for the Diagnosis of Asthma in Adults. Eur Respir J. 2022 Feb 15:2101585. doi: 10.1183/13993003.01585-2021. Epub ahead of print. PMID: 35169025.

Sparreman Mikus M ET AL. U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group and the BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation. Eur Respir J. 2022 Feb 17;59(2):2100142. doi: 10.1183/13993003.00142-2021. PMID: 34737220; PMCID: PMC8850689.

Edgerley S, Zhu R, Quidwai A, Kim H, Jeimy S. Telemedicine in allergy/immunology in the era of COVID-19: a Canadian perspective. Allergy Asthma Clin Immunol. 2022 Feb 21;18(1):16. doi: 10.1186/s13223-022-00657-3. PMID: 35189969.

Hoy SM. Tezepelumab: First Approval. Drugs. 2022 Feb 20. doi: 10.1007/s40265-022-01679-2. Epub ahead of print. PMID: 35184265.
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the pathogenesis of asthma. Tezepelumab (tezepelumab-ekko; TEZSPIRE™) is a first-in-class human IgG2λ monoclonal antibody that inhibits the action of TSLP. Administered subcutaneously, it is being developed by Amgen and AstraZeneca for the treatment of asthma, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria and eosinophilic oesophagitis. Tezepelumab received its first approval on 17 December 2021 as an add-on maintenance treatment for patients aged ≥ 12 years with severe asthma in the USA; it is the only biologic approved for severe asthma with no phenotype (e.g. eosinophilic or allergic) or biomarker limitations. A regulatory assessment of tezepelumab for the treatment of asthma is currently underway in the EU and Japan. Tezepelumab received orphan drug designation for the treatment of eosinophilic oesophagitis in October 2021 in the USA, and is undergoing clinical development for the treatment of COPD, CRSwNP and chronic spontaneous urticaria. This article summarizes the milestones in the development of tezepelumab leading to this first approval for the add-on maintenance treatment of patients aged ≥ 12 years with severe asthma


Wongsa C, Phinyo P, Sompornrattanaphan M, Krikeerati T, Lumkul L, Thongngarm T. Efficacy and safety of house dust mite sublingual immunotherapy tablet in allergic asthma: A systematic review of randomized controlled trials. J Allergy Clin Immunol Pract. 2022 Feb 15:S2213-2198(22)00133-7. doi: 10.1016/j.jaip.2022.01.046. Epub ahead of print. PMID: 35181547.
Background: House dust mite sublingual immunotherapy (HDM SLIT) effectively treats allergic rhinitis (AR). However, the evidence of HDM SLIT for allergic asthma remained limited.
Objective: To systematically review the efficacy and safety of HDM SLIT tablets in patients with allergic asthma.
Methods: We performed a systematic search through PubMed, Scopus, EMBASE, Web of Science, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM SLIT tablets compared with placebo or no intervention in allergic asthma from their inception date until September 2021. The primary outcome was the reduction in inhaled corticosteroid (ICS) dose. Additional outcomes were asthma control, exacerbation, lung function, quality-of-life, and adverse events (AEs).
Results: There were seven RCTs, 5 studies in allergic asthma (4 in adults and one in children), and 2 in AR with or without asthma. The 6 SQ-HDM effectively reduced ICS dose in well- to partly-controlled mild-to-moderate asthma in 1 RCT. Two RCTs evaluated the efficacy of 6 SQ- and 12 SQ-HDM in reducing asthma exacerbation in partly-controlled moderate-to-severe asthma, and their results were inconsistent. One study in children with mild-to-moderate asthma found no benefit of HDM SLIT. Two RCTs in AR with or without mild-to-moderate asthma showed improvement of asthma symptoms. AEs were primarily local, and anaphylaxis treated with epinephrine was reported in 3 patients.
Conclusion: HDM SLIT tablets tend to effectively reduce ICS use in adults and adolescents with well- to partly-controlled mild-to-moderate allergic asthma with a favorable safety profile.

Sunde RB, Thorsen J, Pedersen CT, Stokholm J, Bønnelykke K, Chawes B, Bisgaard H. Prenatal tobacco exposure and risk of asthma and allergy outcomes in childhood. Eur Respir J. 2022 Feb 17;59(2):2100453. doi: 10.1183/13993003.00453-2021. PMID: 34244319.

Runnstrom MC, Morrison-Porter A, Ravindran M, Quehl H, Ramonell RP, Woodruff M, Patel R, Kim C, Haddad NS, Lee FE. Reduced COVID-19 Vaccine Response in Patients Treated with Biologic Therapies for Asthma. Am J Respir Crit Care Med. 2022 Feb 18. doi: 10.1164/rccm.202111-2496LE. Epub ahead of print. PMID: 35180044.

Sokolowska M, Rovati GE, Diamant Z, Untersmayr E, Schwarze J, Lukasik Z, Sava F, Angelina A, Palomares O, Akdis CA, O’Mahony L, Jesenak M, Pfaar O, Torres MJ, Sanak M, Dahlen SE, Woszczek G. Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID-19. Allergy. 2022 Feb 16. doi: 10.1111/all.15258. Epub ahead of print. PMID: 35174512.

Gurrola J 2nd, Borish L. Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response. J Allergy Clin Immunol. 2017 Dec;140(6):1499-1508. doi: 10.1016/j.jaci.2017.10.006. Epub 2017 Oct 26. PMID: 29106996.
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS affects prognosis and, most importantly, is necessary as the basis for making therapeutic decisions. The need for individualized definitions of pathogenic mechanisms before initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics, where, barring an influence from their off-target anti-inflammatory pharmacologic effects, an understanding of the role of the individual biome predicts likelihood of therapeutic benefit. However, this need for identifying individual phenotypes and endotypes also extends to the agent that is currently considered the mainstay of treatment of CRS, specifically glucocorticoids. As with asthma, it is recognized that a large minority of patients with CRS have a steroid-resistant phenotype, identification of which will preclude use of these agents with their potential side effects. Identification of endotypes is also becoming increasingly imperative because targeted biotherapeutic agents, such as anti-IgE and anticytokine antibodies, are becoming available. These agents are likely to benefit patients in whom the targeted mediator is not only expressed but demonstrably driving a central mechanism in that patient. In summary, the treatment of CRS is at an exciting crossroad. On the positive side, numerous therapeutics are in development that seem likely to have a positive effect in our patients with this condition. The challenge is that these therapies will require targeted individualized treatments based on identifying subjects with the relevant endotype. (J Allergy Clin Immunol 2017;140:1499-508.)

Pubblicato in Libra Journal Club.