What Is New In Small Airways Research
By Ves Dimov, M.D.
Allergist/Immunologist, Assistant Professor of Medicine and Pediatrics
University of Chicago
Web Content Editor, WAO Small Airways Working Group
Posted: 7 September 2012
Effect of childhood asthma and inhaled steroid on adult height: 1.2 cm lower height with budesonide vs. placebo
The use of inhaled glucocorticoids (ICS) for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.
This study published in the NEJM measured adult height in 943 participants in the Childhood Asthma Management Program (CAMP) at age 25. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil (not available in the U.S. since 2010), or placebo daily for 4 to 6 years.
Mean adult height was 1.2 cm lower in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower in the nedocromil group than in the placebo group. A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (−0.1 cm for each microgram per kilogram of body weight) (P=0.007). The difference between ICS and placebo was noted only during the first two years of therapy and it was not progressive.
The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative.
This study shows that more severe asthma that requires treatment with ICS is associated with lower height as an adult. Many chronic diseases during childhood affect adult height and asthma is no exception. A longer time since asthma diagnosis and atopy (any positive skin test) were independent risk factors for shorter adult height. When asthma and atopy impair growth, the deficit may persist into adulthood. The conclusion is not to "stop" the use of ICS but to use the lowest effective ICS dose for symptom control, which is in agreement with the current asthma guidelines.
Kelly HW, Sternberg AL, Lescher R, Fuhlbrigge AL, Williams P et al for the CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. New England Journal of Medicine 2012; 367: 904-912. doi:10.1056/NEJMoa1203229
Image source: FDA and Wikipedia, public domain
Immune response modifiers in the treatment of asthma: A PRACTALL document of AAAAI and EAACI
Five percent to 10% of patients with asthma have severe disease that is not responsive to mainstream controller medications such as inhaled steroids. Only 13% of this group meet the criteria for treatment with omalizumab, the only available FDA-approved immune response modifiers (IRM) approved for asthma. Asthma is a complex variable heterogeneous disease. A new approach attempts to divide asthma into distinct entities based not only on clinical presentations but also specific mechanisms, such as asthma endotypes.
IRMs in the treatment of asthma and atopic disorders have not been as successful as anticipated by many or compared with their use in patients with rheumatic diseases. However, a subset of patients may still benefit from IRMs. A good example is anti–IL-5 (mepolizumab) which showed improvement in patients with eosinophilic refractory asthma. At the same time, we must continue to be vigilant for adverse events while studying IRMs.
Advances in the bioengineering of monoclonal antibodies (mAbs), fusion proteins, and small molecules that can be taken orally will be important steps in improving outcomes. Some combination biologics that target more than 1 cytokine receptor or cytokine, such as pitrakinra, may be more successful.
The development of new biomarkers will be critical in identifying patient endotypes that would benefit from specific IRMs. For example, blood eosinophil counts and serum periostin levels served was biomarkers that identified asthma endotypes that would respond to anti–IL-13 mAb (lebrikizumab).
This state of the art review is authored by the leaders in the field of immune response modifiers (IRS) in the treatment of asthma. Its free full text makes it an essential read for all physicians who want to gain an insight into the future of asthma therapies.
Ballow M, Akdis CA, Casale TB, Wardlaw AJ, Wenzel SE et al. Immune response modifiers in the treatment of asthma: A PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. The Journal of Allergy and Clinical Immunology 2012; 130(2): 311-324.
Full Text, Free
A new subset of severe asthma manifests with granulomatous pathology: "asthmatic granulomatosis"
This case series from the University of Pittsburgh, USA included 19 patients (17 women and 2 men) meeting severe asthma definition, requiring daily systemic corticosteroid (CS) use, with inconsistent abnormalities on chest CT scans.
The pathology of 10 of the 19 cases revealed small airway changes consistent with asthma (eosinophilia, goblet cell hyperplasia), but with the unexpected finding of interstitial non-necrotizing granulomas. They had no evidence for hypersensitivity pneumonitis, but 70% of cases had a personal or family history of autoimmune-like disease.
The 10 cases were treated with azathioprine, mycophenolic acid, methotrexate or infliximab. Nine of 10 showed decreased CS requirements and improved or maintained FEV1 despite lower CS doses. A subset of severe "asthma" manifests a granulomatous pathology which the study authors called "asthmatic granulomatosis". Identification of this disease requires an invasive approach such as thoracoscopic biopsy. The risks associated with the biopsy may be warranted considering that immunosuppressants lead to improvement in this subsets of patients with severe asthma.
Asthma is a heterogeneous condition and this case series adds "asthmatic granulomatosis" to the list of asthma subsets. Further studies are needed to confirm its existence.
Wenzel SE, Vitari CA, Shende M, Strollo DC, Larkin A, Yousem SA. Asthmatic granulomatosis: A novel disease with asthmatic and granulomatous features. American Journal of Respiratory Critical Care Medicine 2012; Published online ahead of print 5 July. doi: 10.1164/rccm.201203-0476OC
Posted: 7 September 2012