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Background: Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. Objectives: To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). Design: This was a single-center, retrospective, observational cohort study. Methods: We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. Results: Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). Conclusion: BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation. [ABSTRACT FROM AUTHOR]

Refractory asthma in children seriously affects their lung function and quality of life. There are no guidelines for the diagnosis and treatment of refractory asthma in children in China. This article reviews the research progress on childhood refractory asthma in terms of genetic, environmental, socio-psychological factors. Through genetic testing and biological indicators, early identification of refractory asthma in children and individualized treatment based on molecular level, combined with the control of environmental factors and psychosocial factors, provide new ideas for the prevention and control of refractory asthma in children. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential molecular mechanisms involved in refractory asthma in an animal model, and the potential therapeutic effect of MAPK1 knockdown on the disease. Methods: Eighteen female Institute of Cancer Research (ICR) mice, aged 8 - 10 weeks, were randomly divided into three groups: control, asthma model and refractory asthma, with 6 mice in each group. The expression of MAPK1 was knocked down in mice using an adenoviral vector. Subsequently, the methylation levels of MAPK1 promoter in mouse lung tissue were determined using methylation assays. Hematoxylin and eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used to determine inflammatory and histological changes in lung tissues. Levels of immune cells were determined using flow cytometry, while Western blotting was used to measure the protein expression levels of ERK1/2, JNK, MEK1/2 and p38. Results: Methylation assay results show that mean methylation level of cg11335969 locus was significantly reduced in the refractory asthma mouse model (p < 0.05). The levels of IgG1 and IgM in refractory asthmatic mice were reduced after MAPK1 knockdown. There was a significantly reduced degree of lung lesions in mice (p < 0.05), as was reflected in effectively decreased histopathological changes. Protein levels of ERK1/2, JNK, MEK1/2 and p38, and the levels of neutrophils, dendritic cells, and macrophages were significantly decreased (p < 0.05). Conclusion: There is hypermethylated modification of MAPK1 at cg11335969 site in refractory asthma mouse model. Knockdown of MAPK1 attenuates inflammation and tissue damage, and reverses abnormal immune cell numbers in refractory asthma mice. Thus, MAPK1 inhibition may be a novel strategy for ameliorating immune abnormalities in refractory asthma. [ABSTRACT FROM AUTHOR]

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20–30% of all patients with asthma. Neutrophilic asthma's prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: "neutrophilic asthma", "non-type 2 asthma" and "paucigranulocytic asthma". We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease. [ABSTRACT FROM AUTHOR]

Background: Refractory asthma, which is caused by several factors including neutrophil infiltration is a serious complication of bronchial asthma. We previously reported that nerve growth factor (NGF) is involved in AHR. NGF-derived induction of hyperalgesia is dependent on neutrophils; however, this relationship remains unclear in respiratory disease. In this study, we examined the roles of neutrophils and NGF in refractory asthma. Methods: Using intranasal house dust mite sensitization, we established a mouse model of asthma with mixed inflammation (Mix-in). AHR, NGF production and hyperinnervation of the lungs were examined with or without different inhibitory treatments. The levels of the singlet oxygen markers, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE) in the lungs, were measured by liquid chromatography-tandem mass spectrometry. An in vitro experiment was also performed to evaluate the direct effect of singlet oxygen on NGF production. Results: NGF production and hyperinnervation were higher in Mix-in mice than in conventional eosinophilic-asthmatic mice and were positively correlated with AHR. Asthmatic parameters were inhibited by NGF neutralizing Abs and myeloperoxidase (MPO) inhibition. The 10- and 12-(Z,E)-HODEs levels were increased in the lungs and were positively correlated with MPO activity and NGF production. NGF was produced by bronchial epithelial cells in vitro upon stimulation with singlet oxygen. Conclusions: Our findings suggest that neutrophil MPO-derived singlet oxygen induces increased NGF production, leading to AHR and 10- and 12-(Z,E)-HODEs production. These findings may help to develop new therapies targeting this mechanism and to establish a new biomarker for non-type 2 and refractory asthma.

Tao Wang,1,2,&ast; Fa Long,1,&ast; Zhihui Huang,1 Liang Long,1 Wenting Huang,1 Siyu Hu,1 Fengbo Hu,1 Peng Fu,1 Jingfan Gan,1 Hongbo Dong,1 Guomei Yan1 1University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fa Long, University of Chinese Academy of Sciences Shenzhen Hospital, No. 4253, Songbai Road, Guangming District, Shenzhen, 518106, People’s Republic of China, Tel +86-755-27461986, Email longfa_923@163.comObjective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients.Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response.Results: ACQ score (3.19± 1.14 vs 1.26± 0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53± 21.66 vs 66.19± 22.50), FEV1 (1.53± 0.74 vs 1.93± 0.82), and forced vital capacity (FVC) (2.49± 0.86 vs 2.92± 0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions.Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.Keywords: refractory asthma, bronchial thermoplasty, activation, response, correlation

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis marked by eosinophilia and extravascular granulomas, predominantly affecting the respiratory tract. This report details a unique EGPA case in a 6-year-old girl with extensive cardiac involvement, featuring an atypical intracardiac mass suggestive of endomyocardial fibrosis and a concomitant thrombus. The clinical course unfolded in three phases: an initial prodrome with asthma; subsequent peripheral hypereosinophilia; and ultimately systemic vasculitis. Cardiac involvement, notably an intracardiac mass in the right ventricular apex extending into the interventricular septum, underscored the diverse nature of EGPA. The patient fulfilled sufficient criteria outlined by the American College of Rheumatology and the European Alliance of Associations for Rheumatology for an EGPA diagnosis, displaying hypereosinophilia, obstructive airway disease, and biopsy-confirmed inflammation predominantly characterized by extravascular eosinophils. Treatment included high-dose methylprednisolone and cyclophosphamide, which resulted in clinical improvement and inflammatory marker normalization. To halt right ventricular thrombus progression, therapeutic unfractionated heparin was initiated, and she was transitioned to warfarin, which resulted in complete resolution of the cardiac mass. This case highlights the necessity of a multidisciplinary approach for managing complex EGPA manifestations, particularly in pediatrics, and emphasizes the importance of timely intervention in mitigating the impact of cardiac complications associated with EGPA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Emily O’Reilly,1 Deborah Casey,1 Hisham Ibrahim,1 Alice McGrath,1 Tomás McHugh,1 Punitha Vairamani,1 Jill Murphy,1 Barry Plant,1,2 Desmond M Murphy1,2 1Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland; 2Health Research Board Clinical Research Facility, University College Cork, Cork, IrelandCorrespondence: Desmond M Murphy, Department of Respiratory Medicine, Cork University Hospital, Wilton, Cork, Ireland, Email desmond.murphy@hse.ie

Aims: This study aims to investigate the levels and interactions of ezrin, CD44 and MMP-9 proteins in severe asthma patients who are either treatmentresistant or treatment-sensitive. By identifying these potential biomarkers, we aim to enhance our understanding of the disease mechanisms, develop innovative therapeutic strategies, and improve prognostic evaluations for severe asthma. Methods: Blood samples were collected from severe asthma patients at Çukurova University Faculty of Medicine Balcalı Hospital's Chest Diseases Clinic. Patients who did not achieve symptom control despite optimal medication were classified as having severe asthma. Proteomic analyses were performed on proteins extracted from the blood serum, focusing on ezrin, MMP-9, and CD44. Total protein levels were determined using the BCA method, while protein concentrations were measured through Coomassie Blue staining. Results: The proteomic analysis revealed distinct protein expression patterns between treatment-resistant and treatment-sensitive severe asthma patients. While the study primarily focused on overall protein profiles, the data suggests that variations in proteins such as ezrin, CD44, and MMP-9 could play significant roles in the disease mechanism. These findings are promising for future research into the potential of these proteins as biomarkers for severe asthma. Conclusions: The study underscores the potential of total protein profiles in identifying biomarkers for severe asthma. These initial findings highlight the importance of proteins like ezrin, CD44, and MMP-9, providing a promising direction for future research. Understanding these protein patterns could lead to novel therapeutic approaches and improved prognosis for patients with severe asthma. [ABSTRACT FROM AUTHOR]

Refractory asthma (RA) remains poorly controlled, resulting in high health care utilization despite guideline-based therapies. Patients with RA manifest higher neutrophilia as a result of increased airway inflammation and subclinical infection, the underlying mechanisms of which remain unclear. We sought to characterize and clinically correlate gene expression differences between refractory and nonrefractory (NR) asthma to uncover molecular mechanisms driving group distinctions. Microarray gene expression of paired airway epithelial brush and endobronchial biopsy samples was compared between 60 RA and 30 NR subjects. Subjects were hierarchically clustered to identify subgroups of RA, and biochemical and clinical traits (airway inflammatory molecules, respiratory pathogens, chest imaging) were compared between groups. Weighted gene correlation network analysis was used to identify coexpressed gene modules. Module expression scores were compared between groups using linear regression, controlling for age, sex, and body mass index. Differential gene expression analysis showed upregulation of proneutrophilic and downregulation of ciliary function genes/pathways in RA compared to NR. A subgroup of RA with downregulated ciliary gene expression had increased levels of subclinical infections, airway neutrophilia, and eosinophilia as well as higher chest imaging mucus burden compared to other RA, the dominant differences between RA and NR. Weighted gene correlation network analysis identified gene modules related to ciliary function, which were downregulated in RA and were associated with lower pulmonary function and higher airway wall thickness/inflammation, markers of poorer asthma control. Identification of a novel ciliary-deficient subgroup of RA suggests that diminished mucociliary clearance may underlie repeated asthma exacerbations despite adequate treatment, necessitating further exploration of function, mechanism, and therapeutics. [ABSTRACT FROM AUTHOR]

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20–30% of all patients with asthma. Neutrophilic asthma’s prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: “neutrophilic asthma”, “non-type 2 asthma” and “paucigranulocytic asthma”. We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease.

Acute severe asthma, formerly named status asthmaticus, is defined as a life-threatening asthma exacerbation that is refractory to the current standards of treatment such as the use of beta-agonists and epinephrine. This complication of asthma affects up to 15% of individuals with asthma and despite critical care treatment and hospitalization, there remains a staggeringly high 10-18% mortality rate in an intensive care unit setting. The addition of ketamine to the arsenal of acute severe asthma treatment due to its rapid onset, variable routes of administration, and overall improved clinical efficacy in treatment-refractory cases has been well investigated and documented. Ketamine's anti-inflammatory properties, bronchodilatory effects, and well-documented history contribute to its ability to provide a significant clinical asthma score (CAS) reduction and improvement on pulmonary readings, such as peak expiratory flow (PEF), while providing a well-researched adverse effect profile. This article serves to analyze and review the benefits and risks of incorporating ketamine into the standard treatment regimen for patients suffering from acute severe asthma and discusses the implications of such implementation., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Epperson et al.)

Background Refractory asthma is defined as asthma with persistent symptoms or asthma with frequent or serious exacerbations accompanied by persistent airflow obstruction despite high doses of corticosteroids. Patients and methods This study included 88 patients with asthma at Qena University Hospital. All participants in this study underwent full medical history, physical examination, chest radiography, and spirometry with reversibility test. Then patients were classified into controlled and uncontrolled groups according to asthma control test. Results We found that poorly controlled asthma was significantly associated with older age, (33.03±14.3 years for controlled group versus 42.81±12.8 years for uncontrolled group, P

Bronchial thermoplasty (BT) is an upcoming treatment for patients with asthma refractory to traditional pharmacotherapy. BT is an invasive procedure which carries a risk of coughing, wheezing, bronchospasm, and laryngospasm during and after the procedure. Some of these complications can be minimized using better anesthetic techniques during BT. We hereby report a case of a 63-year-old female with poorly controlled asthma posted for BT done under general anesthesia (GA) with supraglottic device. GA provides better working conditions for pulmonologists when compared with sedation. But still there is no consensus on what would be the ideal anesthetic technique for BT procedure. Till the time, considering anesthesiologist and pulmonologist's prospective, GA (total intravenous anesthesia) using supraglottic device would be a preferred choice for a safe and effective anesthetic strategy in BT.

AIM: The aim of this study was to study the clinical characteristic of patient with refractory asthma (RA) from Saudi Arabia. METHODS: This paper prospectively studied in a university hospital factors leading to RA in a cohort of patients who have inadequately controlled asthma or with frequent exacerbations despite optimum controller therapy. It also studied patients with asthma that requires extended periods of oral steroids to control. RESULTS: The mean age was 45.1 years (±9.1) where 74 patients were enrolled in this study with the age group (37-48 years) is having the highest percentage (64.8%). Female patients represented 62.2%. The two major comorbid conditions were allergic rhinitis (54.1%) and gastroesophageal reflux (33.8%). The vast majority (72 patients) had at least one trigger factor for asthma (97.3%). The asthma control test showed that 86.4% had an uncontrolled status. Spirometry showed mild disease in 9.5%, moderate in 47.3%, and severe in 43.2%. Eosinophilia was seen in only 16.2%. Immunoglobulin E level between 70 and 700 μg/L was found in 58.1% of patients. CONCLUSION: RA has certain clinical characteristics and associated comorbid conditions as well as precipitating factors that facilitate the identifications of these cases.

Introduction: Azathioprine is an immune-modulating agent used in the management of autoimmune diseases and in preventing graft rejection. Its role in the management of refractory asthma is not very well-established. Case study: A 47-year-old female with an underlying severe refractory asthma, managed with high dose steroids, was seen as an outpatient. Her course was complicated by frequent asthma exacerbation and severe adverse effects of chronic steroid use. Her symptoms did not respond to standard asthma management per Guidelines for the Diagnosis and Management of Asthma 1. She was tried on other management which included methotrexate and omalizumab injections without success. Azathioprine was started as a steroid-sparing agent following which her symptoms showed dramatic improvement with fewer exacerbations, higher peak flow measurements, and she was able to wean down her daily prednisone dose from 60 mg/day to 5 mg/day. Conclusion: Azathioprine is still an investigational agent for the management of asthma and more research needs to be done to evaluate its role. To our knowledge, this is the second case report which details the therapeutic role of Azathioprine in the management of asthma. [ABSTRACT FROM AUTHOR]

One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions. Humanized anti-human IgE antibody (anti-IgE; omalizumab) was the first biological preparation approved for treating asthma. Based on clinical evidence, treatment with anti-IgE (anti-IgE therapy) has been accepted as a new therapeutic approach for severe allergic asthma in adults since 2009 and in children since 2012 and has been shown to have ~60% efficacy. More recently, a humanized anti-IL-5 antibody (anti-IL-5; mepolizumab) was launched in June 2016 and has attracted great interest due to its potential effects. Several clinical studies are also ongoing to evaluate the biological preparations targeting IL-5 receptor α (IL-5Rα), IL-4 receptor α (IL-4Rα), which is shared by IL-4 and IL-13, thymic stromal lymphopoietin (TSLP) and IL-33. The new strategy with biologics targeting eosinophilic airway inflammation might open a new array for us to overcome severe refractory asthma in the future. [ABSTRACT FROM AUTHOR]

Key Clinical Message We report the case of a 25-year-old woman with a pulmonary artery sling who was misdiagnosed as having childhood-onset refractory asthma for approximately 20 years. The use of computed tomography may be useful for diagnosing this rare condition. [ABSTRACT FROM AUTHOR]

Background The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. Objective We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. Methods Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. Results BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 μm [25th-75th IQR, 4.0-4.7 μm] and 3.9 μm [25th-75th IQR, 3.7-4.6 μm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm 2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm 2 , P = .02), and epithelial neuroendocrine cells (4.9/mm 2 [25th-75th IQR, 0-16.4/mm 2 ] and 0.0/mm 2 [25th-75th IQR, 0-0/mm 2 ], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. Conclusion BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings. [ABSTRACT FROM AUTHOR]

Tracheal webs are rare anomalies that can be either congenital or acquired due to prolonged or traumatic endotracheal intubation. Patients with tracheal webs present with shortness of breath especially during exertion, stridor, and recurrent chest infections. They are often misdiagnosed and treated as bronchial asthma with only minimal relief of symptoms with bronchodilators. This condition can also present as a cause of difficult endotracheal intubations. CT scans of the chest can be used to screen for airway anomalies; bronchoscopy is both diagnostic and therapeutic. Here we present a 34-year-old woman with a tracheal web who had been on treatment for refractory asthma for many years with only partial relief of her symptoms.

Tracheal leiomyoma is an extremely rare benign tumor. It mostly presents in the third decade of life and mostly affects men. Herein, we describe a patient with tracheal leiomyoma which was treated as asthma for 2 years before definite diagnosis. A 41-year-old female with a history of asthma was referred due to dyspnea and refractory cough. On bronchoscopic examination, a tumoral lesion was found in the distal trachea with near total obstruction and histopathologic examination of the bronchoscopic biopsy was inconclusive. The tumor was surgically resected. On the follow-up bronchoscopic examination, the trachea was normal and symptoms were relieved. Histopathologic results were compatible with Leiomyoma. Airway leiomyoma is commonly misdiagnosed as asthma or bronchitis long before a definitive diagnosis. Fiberoptic bronchoscopy is the modality of choice for direct visualization of intraluminal lesions and tissue sampling. Surgical resection is the gold standard approach. The best surgical approach is not clearly determined to date and both endoscopic procedures and surgical resection have been utilized for treatment in case reports. Usually there is a long interval between onset of clinical symptoms and a definite diagnosis. In the case of refractory signs and symptoms to medical treatment, alternative diagnosis should always be considered. • Tracheal leiomyoma is an extremely rare benign tumor. • A 41-year-old female with a history of asthma was referred due to dyspnea and refractory cough. • On bronchoscopic examination, a tumoral lesion was found in the distal trachea with near total obstruction. • Surgical resection is the gold standard approach. [ABSTRACT FROM AUTHOR]

AIM: The aim of this study was to study the clinical characteristic of patient with refractory asthma (RA) from Saudi Arabia. METHODS: This paper prospectively studied in a university hospital factors leading to RA in a cohort of patients who have inadequately controlled asthma or with frequent exacerbations despite optimum controller therapy. It also studied patients with asthma that requires extended periods of oral steroids to control. RESULTS: The mean age was 45.1 years (±9.1) where 74 patients were enrolled in this study with the age group (37–48 years) is having the highest percentage (64.8%). Female patients represented 62.2%. The two major comorbid conditions were allergic rhinitis (54.1%) and gastroesophageal reflux (33.8%). The vast majority (72 patients) had at least one trigger factor for asthma (97.3%). The asthma control test showed that 86.4% had an uncontrolled status. Spirometry showed mild disease in 9.5%, moderate in 47.3%, and severe in 43.2%. Eosinophilia was seen in only 16.2%. Immunoglobulin E level between 70 and 700 μg/L was found in 58.1% of patients. CONCLUSION: RA has certain clinical characteristics and associated comorbid conditions as well as precipitating factors that facilitate the identifications of these cases. [ABSTRACT FROM AUTHOR]

Background: Despite advances in asthma treatment, severe asthma (SA) still results in high morbidity and use of health resources. Our hypothesis was that SA patients would achieve adequate control with a systematic protocol, including oral corticosteroids, budesonide/formoterol maintenance and reliever therapy and a multidisciplinary approach to improve adherence. Methods: Non-controlled (NC) SA patients were enrolled to receive 2 weeks of oral corticosteroids and 12 weeks of formoterol + budesonide. Assessments included asthma control questionnaire (ACQ), asthma control test (ACT), daily symptom diary, lung function and health-related quality of life (HRQoL) questionnaires. Results: Of 51 patients, 13 (25.5%) achieved control. NC patients had higher utilization of health resources and higher exacerbation rates. Both controlled (C) and NC patients had significantly reduced ACQ scores after oral corticosteroid treatment. After 12 weeks, C patients continued improving. NC patients did not have significant changes. A similar pattern was found regarding lung function, use of rescue medication, and days free of symptoms. After 2 weeks of oral corticosteroids, an increase occurred in those who achieved the ACQ cut off; however, 53.8% of C patients had an ACQ < 1.57 versus 21.1% of NC patients (p = 0.03). Both groups had low HRQoL at baseline with improvement after intervention. Conclusions: Despite rigorous, optimized follow-up treatment, 75% of SA patients did not achieve adequate symptom control and presented with impaired quality of life. Conversely, application of a low-cost, easy to implement systematic protocol can prevent up to 25% of SA patients from up-titrating to new and complex therapies, thus reducing costs and morbidity. Trial registration: Retrospectively registered at ClinicalTrial.gov on 22 February 2010 (NCT01089322). [ABSTRACT FROM AUTHOR]

Bronchial asthma is an inflammatory disorder of airways characterized by hyper-responsiveness to a wide range of triggers and is associated with variable airflow obstruction that remits spontaneously or with the treatment. Several phenotype of asthma not responding to the currently acceptable standard therapy of high dose inhaled gluco-corticosteroids along with along acting β2 agonists come under the purview of refractory asthma. This condition is a heterogeneous and complex disease that requires a multi-disciplinary approach to identify accurately various sub-phenotypes to enable improved understanding of the pathogenesis and development of effective management strategies including use of novel methods and targeted therapy. [ABSTRACT FROM AUTHOR]

Bronchial thermoplasty (BT) is an upcoming treatment for patients with asthma refractory to traditional pharmacotherapy. BT is an invasive procedure which carries a risk of coughing, wheezing, bronchospasm, and laryngospasm during and after the procedure. Some of these complications can be minimized using better anesthetic techniques during BT. We hereby report a case of a 63-year-old female with poorly controlled asthma posted for BT done under general anesthesia (GA) with supraglottic device. GA provides better working conditions for pulmonologists when compared with sedation. But still there is no consensus on what would be the ideal anesthetic technique for BT procedure. Till the time, considering anesthesiologist and pulmonologist's prospective, GA (total intravenous anesthesia) using supraglottic device would be a preferred choice for a safe and effective anesthetic strategy in BT. [ABSTRACT FROM AUTHOR]

Two recent phase III trials in patients with severe eosinophilic asthma have shown that anti-interleukin 5 (IL-5) therapy with mepolizumab reduces the frequency of asthma attacks, improves symptoms and allows patients to reduce oral glucocorticoid use without loss of control of asthma. An earlier large 616 patient Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) study had shown that the only variables associated with treatment efficacy were a prior history of asthma attacks and the peripheral blood eosinophil count. The link between blood eosinophil counts and treatment efficacy is biologically obvious given that IL-5 has a pivotal role in eosinophil production, proliferation and chemotaxis. It is also clinically relevant as the blood eosinophil count is routinely measured and thus readily available in patients with asthma. Recognition of the link between airway or blood eosinophilia and treatment response was also important in the clinical testing of the alternative IL-5 blocker, such as reslizumab, which is currently being evaluated in a phase III randomized controlled trial (RCT) after having shown to improve lung function, improve symptom score and reduce sputum eosinophilia in a smaller phase IIb study. In addition, benralizumab, an IL-5α receptor blocker, has shown good effects in a phase IIb RCT with patients with severe asthma that had sputum eosinophilia and more recently in a phase IIa trial with patients with eosinophilic chronic obstructive pulmonary disease. Therefore anti-IL-5 treatment seems generally effective in eosinophilic asthma, either assessed by blood or airway eosinophilia. This factor together with the impressive clinical efficacy and good safety profile make anti-IL-5 (mepolizumab, reslizumab) and benralizumab (anti-IL-5 receptor α) very promising drugs for the treatment of patients with severe eosinophilic asthma, a subgroup that is in desperate need of better treatments. [ABSTRACT FROM AUTHOR]

Status asthmaticus is an acute, intractable asthma attack refractory to standard interventions that can lead to progressive respiratory failure. Successful management requires a fundamental understanding of the disease process, its clinical presentation, and proper evaluation. Treatment must be instituted early and is aimed at reversing the airway inflammation, bronchoconstriction, and hyper-reactivity that often lead to lower airway obstruction, impaired ventilation, and oxygenation. Most patients are effectively treated with standard therapy including beta2-adrenergic agonists and corticosteroids. Others necessitate adjunctive therapies and escalation to noninvasive ventilation or intubation. We will review the pathophysiology, evaluation, and treatment options for pediatric patients presenting with status asthmaticus with a particular focus on refractory status asthmaticus treated with volatile anesthetics. In addition, we include a proven approach to the management of these patients in the critical care setting, which requires close coordination between critical care and anesthesia providers. We present a case series of three patients, two of which have the longest reported cases of continuous isoflurane use in status asthmaticus. This series was obtained from a retrospective chart review and highlights the efficacy of the volatile anesthetic, isoflurane, in three pediatric patients with refractory life-threatening status asthmaticus. [ABSTRACT FROM AUTHOR]

Introduction: There is evidence that parameters obtained from exhaled breath condensate (EBC) reflect changes in the level of the airway lining fluid. The telation between exhaled nitric oxide (NO) and EBC inflammatory markers has not been analyzed in the context of the inflammatory profile in the airways in asthmatic children. Aim: To show the cytokine profile in EBC of children with severe/refractory asthma as well as correlations between the fractional exhaled NO (FeNO) level and cytokine concentrations. Material and methods: The study population consisted of eight children aged 8 to 17 years with IgE-dependent, severe/refractory asthma with a duration of at least 2 years. This was an observational study, the first consecutive eight patients with asthma symptoms on the day of the study visit, when EBC samples were obtained. Results: The inter-subject variability of study cytokines ranged from 8.6 to 54.6. Cytokines with coefficient of variation < 20% were: interferon-γ, interleukins IL-2, IL-7, IL-15, IL-16, monokine induced by interferon γ (MIG) and tumor necrosis factor α. We showed a significant positive correlation between the FeNO level and crucial mediators in asthma development and progression (IL-2, MCP-1), and potent markers of airway remodeling (PDGFBB, TIMP-2). All correlations between two different variables were controlled for the effects of age, forced expiratory volume in 1 s and number of asthma exacerbations during last 12 months. Conclusions: The profiling of cytokine expression in EBC can be reproducibly performed in children with severe/ refractory asthma. When treating asthma in children, the FeNO level should be monitored as a prevention strategy of the progression of the remodeling leading to refractory/severe asthma. Exhaled breath condensate may be a useful tool to phenotype asthma via a non-invasive approach. [ABSTRACT FROM AUTHOR]