Airway pathology in severe asthma is related to airflow obstruction but not symptom control

Allergy ◽  
2017 ◽  
Vol 73 (3) ◽  
pp. 635-643 ◽  
Author(s):  
D. S. Ferreira ◽  
R. M. Carvalho-Pinto ◽  
M. G. Gregório ◽  
R. Annoni ◽  
A. M. Teles ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Symptom Control ◽  
Airflow Obstruction ◽  
Airway Pathology

scholarly journals Corticosteroid Insensitivity Persists in the Absence of STAT1 Signaling in Severe Allergic Airway Inflammation

2021 ◽  
Author(s):  
Brandon W. Lewis ◽  
Devine Jackson ◽  
Stephanie A Amici ◽  
Joshua Walum ◽  
Manel Guessas ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Mucous Cell ◽  
Airflow Obstruction ◽  
Allergic Airway Inflammation ◽  
Corticosteroid Treatment ◽  
Cell Infiltration ◽  
Eosinophil Infiltration ◽  
Th1 Cell ◽  
Airway Pathology

Corticosteroid insensitivity in asthma limits the ability to effectively manage severe asthma, which is characterized by persistent airway inflammation, airway hyperresponsiveness (AHR), and airflow obstruction despite corticosteroid treatment. Recent reports indicate that corticosteroid insensitivity is associated with increased interferon-gamma (IFN-g) levels and T-helper (Th) 1 lymphocyte infiltration in severe asthma. Signal Transducer and Activator of Transcription 1 (STAT1) activation by IFN-g is a key signaling pathway in Th1 inflammation, however its role in the context of severe allergic airway inflammation and corticosteroid sensitivity remains unclear. In the present study, we challenged wild type (WT) and Stat1-/- mice with mixed allergens (MA) augmented with c-di-GMP, an inducer of Th1 cell infiltration with increased eosinophils, neutrophils, Th1, Th2, and Th17 cells. Compared to WT mice, Stat1-/- had reduced neutrophils, Th1 and Th17 cell infiltration. To evaluate corticosteroid sensitivity, mice were treated with either vehicle, 1 or 3 mg/kg fluticasone propionate (FP). Corticosteroid significantly reduced eosinophil infiltration and cytokine levels in both c-di-GMP + MA-challenged WT and Stat1-/- mice. However, histological and functional analyses show that corticosteroids did not reduce airway inflammation, epithelial mucous cell abundance, airway smooth muscle mass, and AHR in c-di-GMP + MA-challenged WT or Stat1-/- mice. Collectively, our data suggest that increased Th1 inflammation is associated with a decrease in corticosteroid sensitivity. However, increased airway pathology and AHR persist in the absence of STAT1 indicate corticosteroid insensitivity in structural airway cells is a STAT1 independent process.

scholarly journals Persistent Airflow Obstruction: A Marker of a Severe Asthma Cohort – Inflammatory, Functional and Pathological Features

2021 ◽  
Author(s):  
Regina Maria Carvalho-Pinto ◽  
Rodrigo Abensur Athanazio ◽  
Diogenes Seraphin Ferreira ◽  
Thais Mauad ◽  
Marisa Dolhnikoff ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Symptom Control ◽  
Airflow Obstruction ◽  
Small Airways ◽  
High Resolution Computed Tomography ◽  
Muscle Area ◽  
Asthma Control Questionnaire

Abstract In our previous severe asthma cohort, 82% had fixed obstruction. Although they had greater airway smooth muscle area with decreased periostin, inflammation and remodeling weren’t associated with symptom control. High-resolution computed tomography (HRCT) and measures of small airways could be important tools for exploring asthma severity. Our aim was to describe characteristics associated to airflow obstruction in our non-controlled severe asthmatics according to obstruction profile. Persistent obstruction subgroups were also evaluated comparing disease severity. Methods: Patients were evaluated using asthma control questionnaire, induced sputum, spirometry, plethysmography, and Single Breath N2 washout test, at baseline, after oral corticosteroid (OC) and at the end of the treatment. They also underwent thorax HRCT and bronchoscopy with endobronchial biopsy.Results: Sixty-two were included and 77.4% classified as having persistent obstruction; 75% and 25% with moderate and severe obstruction, respectively. Pulmonary function values (FEV1) improved in both subgroups, except in severe. Patients with bronchial thickening, according to RB1 WA% and pi10, had significantly higher airway smooth muscle area.Conclusion: Patients with severe obstruction had greater lung function impairment, no response to OC or bronchodilator. This could be explained by airway remodeling characterized by higher airway smooth muscle area and bronchial thickness assessed by thorax HRCT.

scholarly journals Risk factors for death in patients with severe asthma

2014 ◽  
Vol 40 (4) ◽  
pp. 364-372 ◽  
Author(s):  
Andréia Guedes Oliva Fernandes ◽  
Carolina Souza-Machado ◽  
Renata Conceição Pereira Coelho ◽  
Priscila Abreu Franco ◽  
Renata Miranda Esquivel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Asthma Control ◽  
Severe Asthma ◽  
Airflow Obstruction ◽  
Care Facility ◽  
Health Care Facility ◽  
Control Program ◽  
Male Gender ◽  
Respiratory Causes

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality.

scholarly journals Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215168
Author(s):  
David J Jackson ◽  
John Busby ◽  
Paul E Pfeffer ◽  
Andrew Menzies-Gow ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Symptom Control ◽  
Unmet Need ◽  
High Dose ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Exacerbation Rate ◽  
The Uk ◽  
Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

Acute severe asthma (status asthmaticus)

2019 ◽  
Vol 40 (6) ◽  
pp. 406-409 ◽  
Author(s):  
Neha T. Agnihotri ◽  
Carol Saltoun
Keyword(s):  
Pulse Oximetry ◽  
Severe Asthma ◽  
Status Asthmaticus ◽  
Inhaled Corticosteroids ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Beta Agonist ◽  
Medical Emergency ◽  
Acute Severe Asthma ◽  
Breath Sounds

Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy. It is a medical emergency that requires immediate recognition and treatment. Albuterol in combination with ipratropium bromide in the emergency department (ED) has been shown to decrease the time spent in the ED and the hospitalization rates. The benefits of ipratropium are not sustained after admission to the hospital. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6 to 12 hours. Viral respiratory infections are a common trigger for acute asthma; other causes include medical nonadherence, allergen exposure (especially pets and mold [e.g., Alternaria species]) in individuals who are severely atopic, nonsteroidal anti-inflammatory exposure in patients with aspirin allergy, irritant inhalation (e.g., smoke, paint), exercise, and insufficient use of inhaled or oral corticosteroids. The patient's history should focus on the acute assessment of asthma control and morbidity, including current use of oral or inhaled corticosteroids; the number of hospitalizations, ED visits, intensive care unit admissions, and intubations; the frequency of albuterol use; the presence of nighttime symptoms; activity intolerance; current medications; exposure to allergens; and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, difficulty speaking, refusal to recline < 30°, a pulse of >120 beats/min, and decreased breath sounds. More objective measures of airway obstruction via peak flow or forced expiratory volume in 1 second and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values of >90% are reassuring, although CO2 retention and a low partial pressure of oxygen may be missed.

Correlation of matrix‐related airway remodeling and bradykinin B1 receptor expression with fixed airflow obstruction in severe asthma

Allergy ◽  
2020 ◽  
Author(s):  
Francesca Bertolini ◽  
Vitina Carriero ◽  
Michela Bullone ◽  
Andrea Elio Sprio ◽  
Ilaria Defilippi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Receptor Expression ◽  
B1 Receptor ◽  
Bradykinin B1 Receptor ◽  
Fixed Airflow Obstruction

scholarly journals Recommendations following a modified UK-Delphi consensus study on best practice for referral and management of severe asthma

2021 ◽  
Vol 8 (1) ◽  
pp. e001057
Author(s):  
David J Jackson ◽  
Claire Butler ◽  
Rekha Chaudhuri ◽  
Katie Pink ◽  
Robert Niven ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Working Group ◽  
Symptom Control ◽  
Standards Of Care ◽  
Patient Questionnaire ◽  
High Dose ◽  
Delphi Consensus ◽  
Asthma Patients ◽  
The Uk ◽  
Very High

IntroductionSevere asthma affects an estimated 3%–5% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as high dose of inhaled and systemic steroids used to treat it. The introduction of specialist asthma services across the UK has attempted to improve quality of care and ensure that patients undergo a full systematic assessment prior to initiation of advanced biological therapies. However, improvements are required in the patient pathway to minimise avoidable harm.ObjectivesTo define standards of care in areas where the evidence base is lacking through patient and healthcare professional (HCP) consensus.MethodsThe precision UK National Working Group of asthma experts identified 42 statements formed from 7 key themes. An online four-point Likert scale questionnaire was sent to HCPs working in asthma throughout the UK to assess agreement (consensus) with these statements; a subset of the statements formed a patient questionnaire. Consensus was defined as high if ≥75% and very high if ≥90% of respondents agreed with a statement.ResultsA total of 117/197 responses (59.3% response rate) were received from severe asthma patients (n=15) and HCPs (n=102) including respiratory physicians, respiratory nurse specialists, respiratory pharmacists, specialist physiotherapists and general practitioners. Consensus was very high in 25 (60%) statements, high in 12 (29%) statements and was not achieved in 5 (12%) statements. Based on the consensus scores, the precision UK National Working Group derived 10 key recommendations. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures.ConclusionsImplementation of these 10 recommendations across the severe asthma pathway in the UK has the potential to improve outcomes for patients by reducing delays to assessment and initiation of advanced phenotype-specific therapies.

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