September 2005 World Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. DIFFERENCES IN AIRWAY REMODELING BETWEEN SUBJECTS WITH SEVERE AND MODERATE ASTHMA
These authors obtained endobronchial biopsy specimens from 15 subjects with severe and 13 subjects with moderately severe asthma. They found that the airway smooth muscle area (SMA) was greater in subjects with severe than moderate asthma and the distance between the epithelial and airway SMA layers was less in the severe group. Subepithelial fibrosis was greater in subjects with severe asthma but statistically insignificant. IL-8 and eotaxin but not RANTES expression were increased in SMA of severe asthmatics compared to moderate asthmatics. Smooth muscle alteration is the key structural change associated with remodeling. Editor's comment: Patients with severe asthma may have more remodeling than those with less severe asthma. Pepe C, et al. J Allergy Clin Immunol 2005; 116: 544.
2. DOES GERD TREATMENT IMPROVE ASTHMA OUTCOMES?
Two-hundred seven patients in a multicenter, double-blind, randomized, placebo-controlled trial received usual asthma care including an inhaled corticosteroid (ICS). Patients had acid reflux symptoms and moderate-to-severe persistent asthma and either received lansoprazole, 30 mg bid, or placebo, bid, for 24 weeks. Daily asthma symptoms, albuterol use, peak expiratory flow, FEV1, FVC, and investigator assessed asthma symptoms at 24 weeks did not improve with treatment vs placebo. However, asthma quality of life improved and the treated group had less exacerbations and oral corticosteroid exacerbations. Editor's comment: Treatment of GERDmatters in asthma outcomes. Littner MR, et al. Chest 2005; 128: 1128.
3.PERIPHERAL BLOOD LEUKOCYTES (PBL) IN ASPIRIN-SENSITIVE ASTHMATICS
PBL in aspirin-sensitive (AS) asthmatics generate 15-hydroxyeicosateraenoic acid (15-HETE) when challenged with aspirin in vitro. PBL were obtained from 43 AS patients with asthma and rhinosinusitis, 35 aspirin-tolerant (AT) asthmatics and 17 healthy controls (HC). They were incubated with 2 to 200 µM aspirin (ASA) and 15-HETE measured. There was a significant mean increase of +421% of 15-HETE in ASA patients compared to controls. The sensitivity of the test for confirmation of ASA-sensitivity was 83% and the specificity 82%. The positive predictive value was 0.79 and negative predictive value was 0.86. Editor's comment: This in vitro test may identify and exclude aspirin-sensitive asthmatic patients. Kowalski ML, et al. Allergy 2005; 60: 1139.
4. REGULAR VS AD-LIB ALBUTEROL FOR PATIENTS HOSPITALIZED WITH ACUTE ASTHMA
Sixty-two hospitalized patients with acute asthma were randomized to receive either albuterol nebulizations (regular albuterol group) or saline solution nebulization (ad-lib group) every 4 hr with management of breakthrough symptoms with albuterol metered-dose inhaler or nebulizations for both groups. Patients were otherwise treated similarly. There were no significant differences in length of hospitalization, rate of improvement in peak flow, or symptoms between the two groups. Editor's comment: Metered dose-inhaler, used as needed, seem to be as effective as the regular neubulization of albuterol in the treatment of acute asthma. Chandra A, et al. Chest 2005; 128: 1115.
5. GLUCOCORTICOID RECEPTOR NUCLEAR TRANSLOCATION IN AIRWAY CELLS AFTER INHALED LONG ACTING BETA-AGONIST (LABAs) & GLUCOCORTICOIDS (COMBINATION THERAPY)
There is clinical evidence that combination therapy in asthma is the treatment of choice. This article indicates that glucocorticoid receptors nuclear translocation is enhanced in human airway cells using combined therapy. In vitro, salmeterol enhanced fluticasone propionate (FP) effects on glucocorticoid receptor (GR) nuclear translocation in epithelial and macrophage-like airway cell lines. In addition, the combination of two drugs enhanced glucocorticoid response element (GRE)-luciferase reporter gene activity and mitogen-activated protein kinase phosphatase 1 (MKP-1) and secretory leuko-proteinase inhibitor (SLPI) gene induction. These authors confirm that GR nuclear translocation may underlie the complementary interactions between these two drugs. Editor's comment: This in vitro evidence explains why LABAs seem to enhance the effects ofglucocorticoids in vivo. Usmani OS, et al. Am J Respir Crit Care Med 2005; 172: 704.
6. PREVENTION OF EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WITH TIOTROPIUM
Twenty-six Veterans Affairs medical centers participated in a randomized, double-blind study of 1,829 patients with moderate to severe COPD to determine the efficacy of once-daily tiotropium (18 µg) vs placebo for 6 months to decrease the number of COPD exacerbations and the percentage of patients with a COPD-related hospitalization. Tiotropium significantly reduces the percentage of subjects experiencing one or more exacerbations and results in a non statistically significant trend for decreased hospitalization. Editor's comment: Tiotropium, with or without a long acting beta-agonist, appears to be the treatment of choice for COPD. Niewoehner DE, et al. Ann Intern Med. 2005; 143: 317.
7. DETECTION OF FISH ANTIGENS AEROSOLIZED DURING FISH PROCESSING USING NEWLY DEVELOPED IMMUNOASSAYS
This multi-national study outlines a process whereby aerosolized fish proteins in seafood processing facilities can be monitored. Fish specific ELISA assays were developed which detect 0.5 µg/ml of fish allergens. ELISA inhibition assays are able to differentiate between two different fish species and do not recognize a crustacean species. Thus, these ELISA-based assays are sensitive and specific to quantify and differentiate exposure levels to fish antigens during fish processing. Editor's comment: These assays can detect fish allergens and possibly could be used to prevent fish induced occupational asthma.Lopata AL, et al. Int Arch Allergy Immunol 2005; 138: 21.
8. RHINOVIRUS ILLNESSES DURING INFANCY PREDICT SUBSEQUENT CHILDHOOD WHEEZING
Two hundred and eighty-five children genetically at high risk to develop allergic diseases were evaluated from birth to 3 years of age to determine if viral respiratory infections during infancy increase the risk to develop subsequent wheezing and/or allergic diseases in early childhood. Genetic and environmental factors that could modify the risk of infection and wheezing prevalence were also analyzed. In this population of children, the occurrence of symptomatic rhinovirus illness during infancy was the most significant risk factor for pre-school childhood wheezing and subsequent childhood asthma. Editor's comment: Viruses, in this case rhinoviruses, appear to be an important etiologic agent for childhood asthma. Lemanske RF, et al. J Allergy Clin Immunol 2005; 116: 571.
9. HOSPITALIZATION FOR RSV BRONCHIOLITIS BEFORE 12 MONTHS OF AGE & SUBSEQUENT ASTHMA, ATOPY & WHEEZE: A LONGITUDINAL BIRTH COHORT STUDY
Data from a large population based, birth-cohort study, the Avon Longitudinal Study of Parents and Children (UK), were used to compare outcomes of children according to whether or not they had been admitted to the hospital in the first 12 months of their life with RSV-proven bronchiolitis. Asthma outcomes were measured. RSV bronchiolitis was associated with subsequent wheezing and asthma but not with development of atopy by age 7 years. Editor's comment: This article illustrates the importance of RSV in the pathogenesis of asthma. Henderson J, et al. Pediatr Allergy Immunol 2005; 16: 386.
10. THIS ENTIRE ISSUE OF PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY IS DEVOTED TO AIRWAY RESPONSES TO RESPIRATORY VIRUSES
Many different subjects about airway responses to respiratory viruses are included in this document. Some include: "Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model"; "Acute and Chronic Airway Responses to Viral Infection: Implications for Asthma and Chronic Obstructive Pulmonary Disease"; "Cytokines and Respiratory Syncytial Virus Infection"; "Overview of Virus-Induced Airway Disease"; and "Heterogeneity of the Association between Lower Respiratory Illness in Infancy and Subsequent Asthma". Editor's comment: This special issue reviews the importance of viral infection in the pathogenesis of asthma. Boushey H, et al. (scientific committee). Proc Am Thorac Soc 2005; 2: 107.
11. TWO ARTICLES REVIEW AIRWAY REMODELING
Alterations in the structure and function of airway smooth muscle, epithelium, blood vessels, and mucus glands could explain this phenomenon. In a second editorial, airway smooth muscle is postulated to be the modulator of airway remodeling in asthma. Editor's comment: These are up-to-date articles on an airway remodeling in asthma. Great reading! J Allergy & Clin Immunol: 1) Pascual RM, et al. 2005; 116: 477. 2) Lazaar AL, et al. 2005; 116: 488.
12.HOW EFFECTIVE IS ENVIRONMENTAL CONTROL FOR ALLERGIC RHINITIS AND ASTHMA - AN ARIA UPDATE
Excellent position paper on the effectiveness of altering the indoor environment to treat allergic rhinitis and asthma. This manuscript reviews the positive and negative evidence for instituting practical measures to reduce dust mite and pet allergen levels. The authors conclude that there is little evidence to support the use of physical and chemical methods, including mattress encasing or HEPA-filters, to control dust mites or pet allergens for adults. In children, such environmental controls may be of some benefit. Editor's comment: Perhaps environmental control is "a lot to do about nothing", at least in comparison to other treatmentmodalities. Custovic A, et al. Allergy 2005; 60: 1112.
13. A SPECIAL ISSUE OF RESPIRATORY CARE IS DEVOTED TO METERED-DOSE INHALERS (MDIs) AND DRY POWDER INHALERS (DPIs) IN AEROSOL THERAPY
Some of the articles include: "History of Aerosol Therapy"; Liquid Nebulization to MDIs to DPIs"; "The Expanding Role of Aerosols in Systemic Drug Delivery, Gene Therapy, and Vaccination"; "Principles of Metered-Dose Inhaler Design"; "The CFC to HFA Transition and Its Impact on Pulmonary Drug Development". Editor's comment: Great reading to learn about the complex science of aerosol therapy. Dhand R, MacIntyre NR (co-chairs). Respir Care 2005; 50; 1138.
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