Fixed Airway Obstruction Research Articles

Clinical characteristics of obese, fixed airway obstruction, exacerbation-prone phenotype and comorbidities among severe asthma patients: a single-center study

BackgroundSevere asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear.MethodsA retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study.ResultsA total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations.ConclusionThe existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Structural and functional features of asthma participants with fixed airway obstruction using CT imaging and 1D computational fluid dynamics: A feasibility study.

Asthma with fixed airway obstruction (FAO) is associated with significant morbidity and rapid decline in lung function, making its treatment challenging. Quantitative computed tomography (QCT) along with data postprocessing is a useful tool to obtain detailed information on airway structure, parenchymal function, and computational flow features. In this study, we aim to identify the structural and functional differences between asthma with and without FAO. The FAO group was defined by a ratio of forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC), FEV1 /FVC <0.7. Accordingly, we obtained two sets of QCT images at inspiration and expiration of asthma subjects without (N = 24) and with FAO (N = 12). Structural and functional QCT-derived airway variables were extracted, including normalized hydraulic diameter, normalized airway wall thickness, functional small airway disease, and emphysema percentage. A one-dimensional (1D) computational fluid dynamics (CFD) model considering airway deformation was used to compare the pressure distribution between the two groups. The computational pressures showed strong correlations with the pulmonary function test (PFT)-based metrics. In conclusion, asthma participants with FAO had worse lung functions and higher-pressure drops than those without FAO.

Allergic fungal airway diseases: analysis of data in asthma patient register

Introduction. Allergy to microscopic fungi (micromycetes), which can colonize the respiratory tract, is associated with an eosinophilic endotype of inflammation and severe disease course. Among the hallmarks of fungal allergy, experts identify fixed airways obstruction, bronchiectasis, and fibrosis. Currently, there has been proposed the term “allergic fungal airways disease” (AFAD), which combines various clinical phenotypes, which pathogenesis is based on IgE-mediated allergic reaction against fungal spores colonizing the respiratory tract. According to this approach, the AFAD group includes severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis (ABPA). A promising direction in AFAD treatment implies the use of genetically engineered biological drugs against T-2 inflammation. The aim of the study was to evaluate the prevalence ofAspergillusspp. sensitization and allergic bronchopulmonaryAspergillosis in patients with asthma.&#x0D; Materials and methods. A retrospective single-center registry study was conducted in the I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russian Federation. The study included 523 patients with asthma of varying severity. The level of total and specific blood serum IgE against aeroallergens, includingAspergillusspp., was analyzed by enzyme immunoassay. The diagnosis of asthma was established in accordance with the recommendations of the GINA working group and the Clinical recommendations of the Ministry of Health of the Russian Federation, fungal sensitization and ABPA — in accordance with the recommendations of the ISHAM working group.Results. During the examination of patients with asthma, sensitization toAspergillusspp. recorded in 16.6% cases, severe asthma with sensitization toAspergillusspp. — in 7.4%, ABPA — in 6.1%. In patients with allergic asthma, the prevalence of sensitization toAspergillusspp. was 22%, severe asthma with sensitization toAspergillusspp. — 10.1%, ABLA — 8.1%. Among patients with ABPA, females (64%) aged 40 years and older prevailed. The major clinical manifestations of ABPA were presented as cough (96%) and shortness of breath (76%), CT scan radiological changes were in a form of bronchiectasis (72%).&#x0D; Conclusion. A high prevalence of sensitization toAspergillusspp. in patients with asthma was found. It is necessary to includeAspergillusspp. into the list of tested allergens while examining patients with chronic lung diseases for timely detection of AFAD and prescription of proper anti-inflammatory or antimycotic therapy.

Association of World Trade Center (WTC) Occupational Exposure Intensity with Chronic Obstructive Pulmonary Disease (COPD) and Asthma COPD Overlap (ACO).

Reported associations between World Trade Center (WTC) occupational exposure and chronic obstructive pulmonary disease (COPD) or asthma COPD overlap (ACO) have been inconsistent. Using spirometric case definitions, we examined that association in the largest WTC occupational surveillance cohort. We examined the relation between early arrival at the 2001 WTC disaster site (when dust and fumes exposures were most intense) and COPD and ACO in workers with at least one good quality spirometry with bronchodilator response testing between 2002 and 2019, and no physician-diagnosed COPD before 9/11/2001. COPD was defined spirometrically as fixed airflow obstruction and ACO as airflow obstruction plus an increase of ≥ 400ml in FEV1 after bronchodilator administration. We used a nested 1:4 case-control design matching on age, sex and height using incidence density sampling. Of the 17,928 study participants, most were male (85.3%) and overweight or obese (84.9%). Further, 504 (2.8%) and 244 (1.4%) study participants met the COPD and ACO spirometric case definitions, respectively. In multivariable analyses adjusted for smoking, occupation, cohort entry period, high peripheral blood eosinophil count and other covariates, early arrival at the WTC site was associated with both COPD (adjusted odds ratio [ORadj] = 1.34, 95% confidence interval [CI] 1.01-1.78) and ACO (ORadj = 1.55, 95%CI 1.04-2.32). In this cohort of WTC workers, WTC exposure intensity was associated with spirometrically defined COPD and ACO. Our findings suggest that early arrival to the WTC site is a risk factor for the development of COPD or of fixed airway obstruction in workers with pre-existing asthma.

CLINICAL, FUNCTIONAL AND IMMUNOLOGICAL CHARACTERISTICS OF SEVERE BRONCHIAL ASTHMA

Bronchial asthma is the most common and socially significant disease in humans. Among patients who cannot achieve control, a special group is patients with severe asthma. Objective: comprehensive assessment of clinical, functional, immunological features and pharmacotherapy of severe bronchial asthma in real clinical practice to optimize basic pathogenetic therapy. Materials and methods: 83 patients diagnosed with severe asthma were examined. Patients with severe asthma are divided into 2 groups: patients with and without fixed airway obstruction. Plasma concentrations of cytokines IL-4, IL-5, IL-9, IL-13, periostin, cathepsin S, TGF- were determined by solid-phase enzyme immunoassay. Immune status was investigated on the NAVIOS Flow Cytometer. Results: In both groups of severe bronchial asthma, we found a decrease in T helper and immunoregulatory index levels with simultaneous increases in cytotoxic T lymphocytes, natural T killers, naive T lymphocytes, activated T and B lymphocytes, and phagocytic index compared to controls. There were no differences in immune status between the groups and the resulting changes were independent of the presence or absence of fixed obstruction. In both study groups, we found an increase in cathepsin S and TGF- in plasma compared to control. We identified the most significant risk factors for the formation of fixed obstruction: taking SABA more than 4 inhalations per day (OR = 4.2) and FeNO concentration more than 20 ppb (OR = 6.0). There was a significant improvement in the clinical condition of patients with severe asthma with fixed obstruction while taking genetically engineered biological therapy for a year. Conclusion: To date, there is no unambiguous idea of the mechanisms of implementation of pathobiochemical reactions in the bronchial wall in severe asthma, which lead to the development of fixed airway obstruction. Severe asthma is variable and depends on the correct choice of management tactics.

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia.

Transforming growth factor-β-associated kinase 1 (TAK1) mediates non-canonical TGF-β signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-β1. However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-β1 concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Asthmatic patients with FAO had much greater sputum TGF-β1 concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-β1 levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre- and post-bronchodilator FEV1/FVC ratio. TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact.

Serum biomarkers of remodeling in severe asthma with fixed airway obstruction and the potential role of KL-6.

Over 3% of asthmatic patients are affected by a particularly severe form of the disease ("severe asthma", SA) which is often refractory to standard treatment. Airway remodeling (AR), which can be considered a critical characteristic of approximately half of all patients with SA and currently thought to be the main mechanism triggering fixed airway obstruction (FAO), seems to be a key factor affecting a patient's outcome. Despite the collective efforts of internationally renowned experts, to date only a few biomarkers indicative of AR and no recognizable biomarkers of lung parenchymal remodeling have been identified. This work examines the pathogenesis of airway and lung parenchymal remodeling and the serum biomarkers that may be able to identify the severe asthmatic patients who may develop FAO. The study also aims to examine if Krebs von den Lungen-6 (KL-6) could be considered a diagnostic biomarker of lung structural damage in SA.

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants

PurposeA1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. Aimto investigate genotype and clinical profile of Greeks with AATD. MethodsSymptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. ResultsIncluded are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5–58.5) years, AAT-levels 0.20(0.08–0.26) g/L, FEV1(%predicted) 41.5(28.8–64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). ConclusionGenotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Clinical, functional, and inflammatory characteristics of asthma among adults aged over 60 years old: a case-control study

ObjectiveThis observational case-control study analyzed the clinical, functional, inflammatory profile, and treatment data of a cohort of patients with asthma who were followed up at the outpatient clinic of a teaching hospital. MethodsPatients who visited the clinic between January 2008 and February 2020 and diagnosed with asthma according to the Global Initiative for Asthma (GINA) criteria were included in the study. Patients were broadly classified into two groups: age <60 or age ≥60 years. The patients were evaluated for asthma control and severity, medications used, comorbidities, smoking status, occurrence of exacerbation, spirometry at the first and last visits, sputum cytology, allergic prick test, and inflammatory cytokine levels. ResultsPatients over 60 years of age had lower asthma control test (ACT) scores, required higher doses of inhaled corticosteroids to achieve asthma control and had worse lung function with fixed airway obstruction, higher number of comorbidities, greater exposure to tobacco, and longer outpatient follow-up than younger patients with asthma. Furthermore, older patients presented with neutrophilia and higher levels of TNFα in the induced sputum as compared to younger patients. ConclusionsThese findings suggest that patients aged ≥60 years of age had a more severe asthma profile and poorer lung function than younger patients with asthma. Furthermore, aging, long-term asthma, comorbidities, and tobacco exposure contributed to an accelerated decline in lung function.

Asthma and Fixed Airways Obstruction: Real Life Aspects

We aimed to evaluate asthmatic patients with fixed airways obstruction (FAO) and to verify the impact of follow-up in an asthma-dedicated outpatient clinic on symptoms control and spirometry compared to asthmatics without FAO. We enrolled 20 asthmatic FAO+ patients and 20 FAO- asthmatics at baseline (T0) and at a one-year follow-up visit (T1). FAO+ and FAO- groups were compared for anamnesis, FEV1, asthma control test (ACT) and their ΔT0-T1. FAO+ and FAO- groups did not differ for age, BMI, pack-years, allergy, T0 blood eosinophils, comorbidities or GINA therapy step at T0 and T1, whereas, in the FAO+ group, we found more patients with a delay >5 years between symptoms onset and correct asthma diagnosis (p < 0.05). ACT at T0 and ΔT0-T1, FEV1 at ΔT0-T1 and number of exacerbations at T0 and ΔT0-T1 did not differ between groups. Despite a widespread perception of FAO, per se, as a severity factor for asthma, we found similar severity profiles and amelioration after one year of treatment in the FAO+ and FAO- groups. The only factor linked to FAO development in our population was a delay in asthma diagnosis from respiratory symptoms onset, which may have led to airway remodeling. Physicians should characterize patients with FAO for avoiding misdiagnosis between asthma and other respiratory diseases and for establishing the appropriate therapy.

Thymic stromal lymphopoietin in bronchial asthma patients of different age groups: correlation with other markers, lung function results and disease control

Objective: to investigate correlation between thymic stromal lymphopoietin and bronchial asthma course and control in patients of different age groups. Materials and methods: one hundred and four patients were included in 1-year long open prospective study. There were three age groups: children (6 –11 y.o., n=38), adolescents (14–17 y.o., n=35) and adults (25 –50 y.o., n=31). we used asthma duration ≥12 months, uncontrolled asthma and acute respiratory infection absence for ≥14 days as inclusion criteria. Clinical history, validated questionnaires, spirometry, common blood count, serum and nasal material to evaluate thymic stromal lymphopoietin were obtained during first visit. Patient were consequently examined twice with 6 months intervals. Statistical analyses included ANOVA (Kruskal-wallis test) and Pearson’s correlation (r). Differences accepted significant with р&lt;0,05. Resuts: prevalence of main risk factors of asthma control lost (poor compliance, obesity, non-atopic phenotype, fixed airway obstruction) was different in age groups. we didn’t find any thymic stromal lymphopoietin in nasal material. Thymic stromal lymphopoietin concentration correlate significantly with duration of uncontrolled asthma in previous 12 months (r=0,74). we have found greater serum thymic stromal lymphopoietin concentration in patients who demonstrated FEV1 below normal at Visit 3. Conclusion. Serum thymic stromal lymphopoietin level can be used as risk factor of asthma future exacerbation and spirometry results decline.

Postinfectious Bronchiolitis Obliterans

Childhood bronchiolitis obliterans (BO) is an uncommon complication that is characterized clinically by persistent and continuous obstructive respiratory symptoms, and has been described secondary to various etiologic factors, including drugs, exposure to toxic fumes, allergic reactions, collagen vascular disease or infections. BO occurs most commonly in children after an episode of acute bronchiolitis and is considered a long-term sequela of viral infection.Postinfectious Bronchiolitis Obliterans (PIBO) is characterized by persistent airway obstruction with functional and radiological evidence of small airway involvement that is in general unresponsive to bronchodilator treatment.Although the condition is relatively rare, and its exact incidence is unknown, it is important to keep it in mind. PIBO is complication of lower respiratory tract epithelial injury, and is often misdiagnosed, delaying recognition and potential treatment. A PIBO diagnosis is usually based on a few factors, including a good medical history, positive clinical findings, and lung function test and imaging results, although biopsy and histopathology remain as the optimum diagnostic approach. There have to date been few studies proposing treatments for the condition, and no accepted protocol exists in literature. There is usually a fixed airway obstruction in PIBO. Various treatment approaches have been extrapolated from studies of post bone marrow transplantations and lung transplant BO. The clinical course is variable, and good supportive therapy is essential, with anti-inflammatory therapy often being employed.

Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA

Although asthma is typically characterized by bronchodilator responsiveness (BDR), fixed airflow obstruction (FAO) occurs in ∼50% of patients with severe asthma. Do FAO/BDR associate with efficacy of omalizumab, a monoclonal antibody that targets IgE? In EXTRA, patients aged 12-75 years with inadequately controlled severe allergic asthma despite high-dose inhaled corticosteroids plus long-acting β2-agonists were randomized to omalizumab (n= 427) or placebo (n= 423) for 48 weeks of treatment. In this post hoc analysis, high/low BDR weredefined as ≥12%/<12% increases in baseline forced expiratory volume in 1 second (FEV1) after bronchodilator administration, respectively. FAO presence (+)/absence (-) were defined as baseline postbronchodilator FEV1/forced vital capacity <70%/≥70%, respectively. Poisson regression/analysis of covariance models were used to estimate exacerbation relative rate reductions (RRRs)/least-squares mean changes in FEV1, respectively. In patients with high BDR, omalizumab reduced exacerbations more than placebo over the 48-week treatment period regardless of FAO status (RRR [95% confidence interval(CI)]: FAO+, 59.8% [17.7-80.4%]; FAO-, 44.3% [16.6-62.8%]). Omalizumab improved FEV1 compared with placebo in the FAO-, high BDR subgroup (FEV1 change from baseline [95% CI] for omalizumab vs placebo, 0.065 L [-0.071to 0.201 L] to 0.236 L [0.112-0.359 L]) across 48 weeks. This was not observed in patients with low BDR, irrespective of FAO. Omalizumab was more efficacious than placebo at reducing exacerbations in patients with high, but not low, BDR, regardless of the presence of FAO. Lung function improvement primarily occurred in FAO-, high BDR patients, suggesting that asthma with low BDR may represent a difficult-to-treat phenotype.

Central airway issues in bronchopulmonary dysplasia.

While there is a very large focus on the abnormalities of parenchymal lung development and extensive efforts to minimize alveolar damage with "gentle ventilation" and noninvasive respiratory support for neonates with bronchopulmonary dysplasia (BPD), there is relatively little consideration for the implications of central airway disease in this patient population. There are significant changes in the structure and conformation of the central airway during the last half of gestation, and premature birth disrupts this natural developmental process. The arrest of maturation results in a smaller airway that is more compliant, easier to deform, and more susceptible to damage. Consequently, neonates with BPD are prone to developing central airway pathology, particularly for patients who require intubation and positive pressure ventilation. Central airway disease can be divided into dynamic and fixed airway obstruction and results in increased respiratory morbidity in neonates with chronic lung disease of prematurity.

Modern understanding of bronchial asthma with fixed airflow obstruction

The review provides data on one of the phenotypes of severe bronchial asthma it is asthma with fixed airway obstruction. According to data published today, there is no single pathway for the formation of fixed airway obstruction in patients with severe asthma. Increasing knowledge of the pathophysiology of fixed airway obstruction, as well as identifying the most significant risk factors, is essential for the successful treatment of such patients. In addition, the development of fixed obstruction is associated with a worse and sometimes fatal prognosis. Expanding the existing views is also necessary to overcome the difficulties of differential diagnosis between bronchial asthma with fixed airway obstruction and bronchial asthma in combination with COPD. All this will optimize the approach to the management of patients with bronchial asthma to prevent the formation of fixed airway obstruction.

Neutrophil gelatinase-associated lipocalin and interleukin-6: Potential biomarker for asthma- COPD overlap, differentiation from asthma and COPD

Asthma-COPD overlap (ACO) is a disorder that combines clinical signs of bronchial asthma and COPD – fixed airways obstruction and/or significant reversibility of the bronchial obstruction, rapid progression, poor quality of life, higher mortality, frequent and severe exacerbations compared to COPD and asthma alone. The aim of our study is to determine the neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-6 (IL-6) plasma levels and to analyze their association with peripheral eosinophilia and exacerbations of patients with asthma-COPD overlap (ACO), Chronic obstructive pulmonary disease (COPD) and asthma. Our results, based on 81 patients, indicate that the plasma levels of NGAL and IL-6 are significantly elevated in ACO and are associated with blood eosinophilia and exacerbations. NGAL and IL-6 may be useful biomarkers for differentiation of patients with frequent exacerbations and ACO.

Neutrophilic asthma: a complex phenotype of severe asthma

Asthma is a common chronic airway disease affecting about 334 million people worldwide, and an estimated 7 million children globally. Approximately 10% of patients with asthma have severe refractory disease, which is difficult to control on high doses of inhaled corticosteroids and other modifiers. Among these, are patients with severe neutrophilic asthma. Neutrophilic asthma is a phenotype of asthma that is very severe and persistent, with frequent exacerbations, and characterized by fixed airway obstruction. It is associated with comorbidities such as respiratory infections, obesity, gastroeosophageal reflux disease, and obstructive sleep apnoea. Immunopathologically, it is characterized by the presence of high levels of neutrophils in the lungs and airways. Neutrophils and the interleukin-17 family of cytokines play a pivotal role in the pathogenesis of severe neutrophilic asthma. Most patients with the disease do not achieve control with high dose inhaled corticosteroids, and probably to novel IgE, interleukin and interleukin monoclonal antibodies.

Prompt Resolution of Chronic Rhinosinusitis with Nasal Polyposis and Chronic Bronchitis After First Dose of Benralizumab

Several mAB therapies are approved for treatment of moderate to severe eosinophilic asthma. Clinical trials investigating their efficacy in chronic rhinosinusitis and nasal polyps are encouraging and continued trials are underway. We present a patient treated with benralizumab for refractory nasal polyps and non-allergic, non-asthmatic chronic respiratory symptoms. His symptoms began after noxious exposure to mold, and were associated with eosinophilic polyp tissue and elevated peripheral eosinophil count. He is a never-smoker, fit and healthy ex-military officer with no history of allergic rhinitis or asthma. A PubMed review of all articles reporting data on the use of biologic therapies for nasal polyps and chronic rhinosinusitis with or without nasal polyposis was conducted. A 53-year-old man had been aggressively treated with 8 courses of antibiotics, oral and topical steroids, sinus surgery, and ICS/LABA for sudden onset and refractory chronic rhinosinusitis with eventual development of recurrent nasal polyps and fixed airway obstruction over a period of 2.5 years. Following the 1st dose of benralizumab his symptoms, nasal polyps, and airway obstruction improved dramatically. Upper airway rhinitis and PND as well as lower airway wheezing resolved within 17 days. After 3 months of treatment his spirometry was unobstructed with normal FEV1 (+24% from baseline), and minimal polyp tissue was visible on endoscopic exam. After 12 months benralizumab therapy was stopped. Physicians should consider a trial of anti-eosinophil mABs in patients with nasal polyps especially if there is evidence of eosinophilic inflammation of the upper or lower airway.

Phenotypes of bronchial asthma during the health resort period and personalized programs of medical rehabilitation

Bronchial asthma (BA) is a relevant social and medical problem in our country and around the world. Currently, phenotypes of the disease are distinguished. One of the original decisions in phenotypes distinguishing is the use of cluster analysis. However, the concept of BA phenotypes at the health resort period of rehabilitation has not yet been formed. To determine the BA phenotypes upon admission of patients to a health resort medical rehabilitation (HRMR) using cluster analysis and to offer personalized rehabilitation programs. 518 patients with asthma who underwent HRMR on the southern coast of Crimea were examined. Each patient received clinical, functional and laboratory examination. HRMR included correction of long-term treatment according to the severity of asthma, climate therapy, respiratory therapy, educational programs, and physiotherapeutic procedures. We applied cluster analysis in order to identify BA phenotypes. Description statistics methods were used for phenotype-cluster characterization, comparative analysis - for determination of reliable phenotypic characteristics and relation of the effectiveness of HRMR and phenotypes. A model of three phenotype-clusters was developed. The first cluster included patients with BA of moderate severity, uncontrolled course, frequent exacerbations, history of atopy, a tendency to obesity, moderately reduced external respiration function, fixed airway obstruction, high adherence to long-term therapy with medium doses of inhaled glucocorticoids (ICS) combined with long-acting β-2 agonists (LABA). Cluster 2 included patients with mild asthma, controlled or partially controlled course of the disease, with rare short exacerbations, late onset, preserved external respiration function and exercise tolerance, but low adherence to long-term therapy with medium and low doses of ICS. Cluster 3 included patients with moderate to severe BA, uncontrolled course, with early onset, frequent and prolonged exacerbations, severe symptoms, significantly reduced external respiration function with fixed obstruction, decreased exercise tolerance, but low adherence to long-term therapy (4th stage) with high doses of ICS in combination with LABA and long-acting anticholinergics. A close relationship was found between phenotypes-clusters and the achieved effects: a significant increase in the control of BA and a high efficiency of rehabilitation in patients of the 1st and especially 3rd clusters and low in the 2nd cluster. The optimal rehabilitation programs for each of the selected cluster phenotypes were determined. The cluster model developed with the help of artificial intelligence has demonstrated high prognostic value in the determination of the effectiveness and change of control over the course of asthma as a result of HRMR. Personalized HRMR programs are suggested.

Risk Factors for Acute Exacerbations in Elderly Asthma: What Makes Asthma in Older Adults Distinctive?

PurposeAsthma in the elderly (EA; ≥ 65 years of age) is increasing, adding a heavy socioeconomic burden to the healthcare system. However, little is known about risk factors associated with acute exacerbations in EA patients. The objective of this study was to investigate risk factors for acute exacerbation in EA compared to non-elderly asthma (NEA).MethodsWe combined data from 3 adult asthma cohorts under a unified protocol and database. Asthmatic patients with regular follow-up during a 1-year period were selected from the cohorts to identify the risk factors predicting acute exacerbations in EA compared to NEA.ResultsWe selected a total of 1,086 patients from the merged cohort. During the observation period, 503 and 583 patients were assigned to the EA and NEA groups, respectively. The exacerbation rate was 31.0% in the EA and 33.2% in the NEA group. Multivariate logistic regression analysis revealed fixed airway obstruction, chronic rhinosinusitis (CRS), and male sex as independent risk factors for exacerbation in the EA group. In the NEA group, exacerbation increased along with an increase in eosinophil count. Bayesian analysis of the interactions among clinical factors revealed that forced expiratory volume in 1 second/forced vital capacity was directly related to exacerbation in the EA group, and eosinophil count was related to exacerbation in the NEA group.ConclusionsWe suggest that fixed airway obstruction and CRS as the important clinical factors predicting acute exacerbations in EA, whereas in NEA, eosinophil count was the strong predictor of exacerbation.