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Near Fatal Asthma: Clinical and Airway Biopsy Characteristics  [PDF]
Richard G. Barbers,Ilias C. Papanikolaou,Michael N. Koss,Ashish Patel,Elton Katagihara,Maggie Arenas,Khalid Chan,Colleen G. Azen,Om P. Sharma
Pulmonary Medicine , 2012, DOI: 10.1155/2012/829608
Abstract: Background. Inflammation and remodeling are integral parts of asthma pathophysiology. We sought to describe the clinical and pathologic features of near fatal asthma exacerbation (NFE). Methods. Bronchial biopsies were collected prospectively from NFE I subjects. Another NFE II group and a moderate severity exacerbation control group (ME II) were retrospectively identified—no biopsies obtained. Results. All NFE II ( ) subjects exhibited remodeling and significant inflammation (eosinophilic, neutrophilic). NFE II group ( ) had a significant history of prior intubation and inhaled corticosteroids usage compared to ME II group ( ). They also exhibited leukocytosis, eosinophilia, and longer hospitalization days. Conclusions. Remodeling, eosinophilic, and neutrophilic inflammation were observed in NFE. NFE is associated with prior intubation and inhaled corticosteroids usage. 1. Introduction Remodeling in asthma refers to structural changes in large and small airways, consisting of subepithelial fibrosis, increased vascularity, increased airway smooth muscle mass, and goblet cell hyperplasia of proximal and distal airways [1, 2]. Remodeling was believed originally to be the cause of refractory asthma, that is, asthma that fails to respond to optimal treatment and is characterized by persistent airflow limitation [3]. However, apart from severe asthma, bronchial biopsy studies have shown the features of remodeling in mild and moderate asthma, as well as in children with asthma and preschool wheezing [4, 5]. Remodeling and persistent inflammation are present in relatively mild and “benign” asthma, but not many data exist regarding the pathologic features in severe asthmatic exacerbations or in near fatal asthma [6]. This study was conducted in order to characterize the clinical and airway biopsy features of asthmatic patients who had a near fatal exacerbation (NFE). The NFE patients are severe asthmatics who presented at the Emergency Department (ED) requiring admission to the Intensive Care Unit (ICU) and were put under mechanical ventilation. We hypothesized that this subgroup of patients was the most likely to exhibit evidence of airway remodeling. This observation would particularly help us how to optimally manage these severely compromised patients; studies in humans but also in animal models yield contradictory results about the effectiveness of anti-inflammatory medication against remodeling [7, 8]. The clinical phenotypes associated with an NFE are, as well, of obvious clinical importance. 2. Materials and Methods 2.1. Study Design We defined two
The Association of Functional (Spirographic and Peak Flow Metric) Characteristics and Clinical Evaluations of Bronchial Asthma Control in Children and Teenagers  [PDF]
Т.I. Eliseeva,N.A. Geppe,I.I. Balabolkin
Sovremennye Tehnologii v Medicine , 2012,
Abstract: The aim of the investigation is to estimate the association of bronchial asthma control level indices according to Asthma Control Questionnaire (ACQ) with indices of peak expiratory flow (PEF) and forced expiratory volume 1-second (FEV1) measured simultaneously with the interviewing. Materials and Methods. There were examined 127 children and teenagers aged 5–17 years with atopic asthma of various levels of asthma control. Apart from standard clinical (including anthropometry), functional, immunologic, allergological examinations, all children underwent questionnaire survey according to ACQ, PEF measurement using peak-flowmetry, and the measurement of basic spirographic indices. Results. There was revealed the correlation relationship between ACQ test indices (in points), for one part, and PEF and FEV1 (in percentage of adequate values) measured in the daytime, for the other part. The correlation coefficient between ACQ and FEV1 was –0.65, p=0.00001, that is higher than the coefficient between ACQ and PEF (r=–0.39; p=0.00001). To estimate the potential contribution of data of functional parameters in the diagnostics of asthma control there was performed discriminative analysis. A part of correctly classified cases relying on functional parameters was 53% for PEF and 66% for FEV1, i.e. the classification of bronchial asthma control level with the assistance of FEV1 monitoring has advantages as compared to PEF measurements.
Clinical Asthma Phenotypes and Therapeutic Responses  [PDF]
M. Zedan,G. Attia,M. M. Zedan,A. Osman,N. Abo-Elkheir,N. Maysara,T. Barakat,N. Gamil
ISRN Pediatrics , 2013, DOI: 10.1155/2013/824781
Abstract: Asthma is a heterogeneous disease that means not all asthmatics respond to the same treatment. We hypothesize an approach to characterize asthma phenotypes based on symptomatology (shortness of breath (SOB), cough, and wheezy phenotypes) in correlation with airway inflammatory biomarkers and FEV1. We aimed to detect whether those clinical phenotypes have an impact on the response to asthma medications. Two hundred three asthmatic children were allocated randomly to receive either montelukast (5?mg at bed time) or fluticasone propionate (100?ug twice daily) for 8 consecutive weeks. Serum concentrations of IL-2Rs, ICAM-1, VCAM-1, total IgE, eosinophilic %, eosinophil cationic protein (ECP), and FEV1 were done before and after treatment to patients and once to controls. Children who have SOB were found to have higher levels of total sIgE, older age, and longer disease duration, and they responded to fluticasone alone. Cough group was found to have higher levels of eosinophilic % and sECP, younger age, shorter disease duration and responded to montelukast alone. Wheezy group showed mixed pattern and responded to both medications. Conclusion. Although there is variability in response to ICS and LTRAs, we did identify characteristics of patient that should guide the clinician in the choice of asthma medications. 1. Introduction Evidence is increasing that asthma is a heterogeneous disease constituted by overlapping separate syndromes with probably different, but yet undefined, causes and natural histories. There is a need to identify each of these groups of patients (the so-called asthma phenotypes), whose clinical and prognostic characteristics and responses to treatment may be heterogeneous between groups and homogeneous within each group [1]. All asthmatics, by definition, share a common physiologic abnormalities of reversible airflow obstruction detected by spirometry, airway hyperreactivity, and symptoms that can include shortness of breath, wheezes, and cough. Despite these shared features, a great heterogeneity was noticed in the severity of airway obstruction, clinical phenotypes, degree of reversibility, and the amount of improvement in response to asthma medicines [2]. These phenotypes include allergic and nonallergic asthma. Other phenotypes defined by clinical or physiological categories (i.e., severity, age at onset, and chronic airway obstruction), by asthma triggers (i.e., viral, exercise, occupational allergens, or irritants), by their pathobiology (i.e., eosinophilic, neutrophilic, and paucigranulocytic asthma), or by their course (i.e.,
N.A. Karoli,A.P. Rebrov,A.A. Roschina
Saratov Journal of Medical Scientific Research , 2008,
Abstract: Peculiarities of arterial hypertension in patients with bronchial asthma give rise to the scientific and clinical interest for investigators. The aim of the present study was to elucidate and compare special characteristics of systemic hypertension in patients with bronchial asthma and arterial hypertension by means of daily blood pressure. 93 patients with bronchial asthma were under study (34 men and 59 women of 40,2 ± 8,93 years old): 21 patients without hypertension, 14 patients with primary hypertension and 58 patients with pulmonary hypertension. 77 patients with essential arterial hypertension (30 men and 47 women of 41,7±4,8years old) constituted the control group. Daily blood pressure monitoring was carried out in all patients. Insufficient night decrease of blood pressure (<10%) in patients with asthma and pulmonary hypertension was twice as much than in patients from the control group (53,5% and 26% accordingly). Elevation of blood pressure, heart rate, blood pressure variability, pressure load indices were developed to associate with frequency of dispnoea attacks, especially in patients with bronchial asthma and pulmonary hypertension.
Clinical Differentiation Between Resistant Asthma and Chronic Bronchiolitis: Testing a Practical Approach
Mostafa Ghanei,Henry D. Tazelaar,Ali Amini Hari,Mohammadreza Peyman
Iranian Journal Of Allergy, Asthma and Immunology , 2007,
Abstract: Intractable asthma is a challenging clinical problem. This study was conducted to determine whether a subset of patients with Intractable asthma may be misdiagnosed and have a form of bronchiolitis instead and also to determine the effectiveness of macrolide therapy in these patients. Seventy six patients with Intractable asthma were re-treated with recommended maximal doses of oral prednisolone for 5 days, beclomethasone, cromolyn sodium, salbutamol and ipratropium bromide for 30 days. Thirty five patients were considered as unresponsive and constituted the study group. They underwent high-resolution CT (HRCT) scan following which they were offered with video-assisted thoracoscopic surgical biopsy. Group 1 (n= 27) refused biopsy and each was treated with macrolide therapy, while Group 2 (n=8) underwent biopsy, and then received macrolide therapy. The patients were treated and followed for three months. The study group consisted of 27 patients, with a mean age of 46.9 ± 11.1 years. The mean duration of time between the onset of symptoms and the start of this study was 8.1 years. In group 2, no patient had pathologic findings of asthma, and 7/8 had a form of bronchiolitis. There was significant improvement in dyspnea, cough and pulmonary function indices at the end of the 3-month in both groups (p< 0.001). Our results suggest that patients with Intractable asthma could be misdiagnosed and some of them have some forms of chronic bronchiolitis. We believe that any patient who does not respond to standard treatments for Intractable asthma should be evaluated with expiratory HRCT; those with significant air trapping should be considered for a course of macrolide therapy or biopsy for better identification of the underlying disease.
Clinical review: Severe asthma
Spyros Papiris, Anastasia Kotanidou, Katerina Malagari, Charis Roussos
Critical Care , 2002, DOI: 10.1186/cc1451
Abstract: Treatment for acute, severe asthma includes the administration of oxygen, β2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative.Bronchial asthma has a wide clinical spectrum ranging from a mild, intermittent disease to one that is severe, persistent, and difficult to treat, which in some instances can also be fatal [1,2,3,4]. Asthma deaths, although uncommon (one in 2000 asthmatics), have increased over the last decades [2], with more than 5000 deaths reported annually in the USA and 100,000 deaths estimated yearly throughout the world [1,2]. Patients at greater risk for fatal asthma attacks are mainly those with severe, unstable disease, although death can occur to anyone if the asthma attack is intense enough [2,3,4]. Most deaths from asthma are preventable, however, particularly those among young persons. Morbidity in
Asthma Control TestTM in Assessment of Clinical Asthma Control
Jordan Minov,Jovanka Bislimovska-Karadzhinska,Tatjana Petrova,Kristin Vasilevska
Macedonian Journal of Medical Sciences , 2009,
Abstract: Background. The goal of asthma treatment is to achieve and maintain control of the disease.Objective. To assess validity and reliability of Asthma Control TestTM (ACT) as a patient-based tool for quantifying the control of the disease in the subjects with persistent asthma. Methods. A cross-sectional study including 396 subjects with persistent asthma drown from a population of treated patients was performed. Evaluation of the examined subjects included completion of the ACT, spirometry, and asthma specialist rating of control. Results. The mean derived ACT score in all study subjects was 19.2±3.3. Prevalence of the study subjects with totally controlled (TC), well-controlled (WC) and not well-controlled (NWC) asthma by derived ACT score was 9.1%, 43.2% and 47.7%, respectively. Results from the spirometry showed that in 45% of the study subjects FEV1 value was less than 80%. Prevalence of the study subjects with TC, WC and NWC asthma by asthma specialist rating was 8.1%, 41.1% and 50.7%, respectively. A strong correlation between the derived ACT scores and asthma specialist rating of control was observed (r = 0.51, P = 0.000). Conclusion. Our data confirm the usefulness of the ACT as a valid and reliable screening tool for asthma control.
The Asthma-COPD Overlap Syndrome: A Common Clinical Problem in the Elderly  [PDF]
Amir A. Zeki,Michael Schivo,Andrew Chan,Timothy E. Albertson,Samuel Louie
Journal of Allergy , 2011, DOI: 10.1155/2011/861926
Abstract: Many patients with breathlessness and chronic obstructive lung disease are diagnosed with either asthma, COPD, or—frequently—mixed disease. More commonly, patients with uncharacterized breathlessness are treated with therapies that target asthma and COPD rather than one of these diseases. This common practice represents the difficulty in distinguishing these disorders clinically, particularly in patients with a history that does not easily differentiate asthma from COPD. A common clinical scenario is an older former smoker with partially reversible or fixed airflow obstruction and evidence of atopy, demonstrating “overlap” features of asthma and COPD. We stress that asthma-COPD overlap syndrome becomes more prevalent with advancing age as patients respond less favorably to guideline-recommended drug therapy. We review the similarities and differences in clinical characteristics between these disorders, and their physiologic and inflammatory profiles within the context of the aging patient. We underscore the difficulties in differentiating asthma from COPD in current or former smokers, share our institutional experience with overlap syndrome, and highlight the need for new research to better characterize and investigate this important clinical phenotype. 1. Introduction The general internist, allergist, and pulmonologist commonly encounter adult patients with clinical features of both asthma and chronic obstructive pulmonary disease (COPD). Differentiating the underlying cause of their symptoms becomes difficult and often leads to blanket therapy directed towards airway hyperreactivity (AHR), airway inflammation, airflow obstruction, and allergic disease. A salient example is an older patient with a history of seasonal allergies and asthma, a current or past smoking history, and progressive symptoms of acute-on-chronic dyspnea. They may demonstrate fixed airflow obstruction or partial reversibility on spirometric testing, an elevated total IgE, and a slightly increased nitric oxide level. Does such a patient have COPD with AHR, remodeled asthma that has progressed to partially reversible or “fixed” airflow obstruction, or overlapping COPD and asthma—the so-called asthma-COPD overlap syndrome? Is some degree of airflow obstruction simply related to natural aging of the lung (a decline in FEV1 exceeding the predicted 25 to 30?mL per year), and should this be treated? These questions beget further questions regarding the need to distinguish the components of asthma-COPD overlap and the associated treatment implications, including drug side effects,
Omalizumab: Clinical Use for the Management of Asthma
Neil C. Thomson and Rekha Chaudhuri
Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine , 2012, DOI: 10.4137/CCRPM.S7793
Abstract: Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting 2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.
Viral asthma: implications for clinical practice  [cached]
Roger Menendez,Michael D Goldman
Journal of Asthma and Allergy , 2010,
Abstract: Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials
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