Acinar effect of inhaled steroids evidenced by exhaled nitric oxide
ABSTRACT The effects of inhaled corticosteroids (ICSs) on distal lung inflammation, as assessed by alveolar nitric oxide concentration (C(A)NO), are a matter of debate. Recently, a theoretic study suggested that acinar airway obstruction that is relieved by ICS treatment and associated with a decrease in fraction of exhaled nitric oxide (FeNO) concentration might, paradoxically, increase C(A)NO. This increase could be a hallmark effect of ICSs at the acinar level.
In the light of this new hypothesis, we studied changes in C(A)NO and FeNO after administration of ICSs.
C(A)NO and FeNO were measured before and after ICS treatment of 38 steroid-naive patients with uncontrolled asthma who showed clinical improvement after ICS therapy.
The average FeNO decreased from 78.3 to 28.9 ppb (P < .001); C(A)NO decreased from 7.7 to 4.3 ppb (P = .009). In 14 subjects (low-slope group), slope (= ΔC(A)NO/ΔFeNO) values (Δ = post-ICS - pre-ICS value) were less than the 95% normal CI (average ΔFeNO = -32.7 ppb and average ΔC(A)NO= +2.9 ppb). In this group, baseline C(A)NO was abnormally low when FeNO was taken into account. In 11 subjects (the high-slope group), the slope was above the normal interval (average ΔFeNO = -42.5 ppb and average ΔC(A)NO = -14.7 ppb).
Opposite patterns (one that was predicted) can indicate peripheral actions of ICSs; this difference might account for conflicting data reported from studies using C(A)NO to determine the peripheral action of ICSs. We show that a low C(A)NO does not preclude distal inflammation.
- The Journal of allergy and clinical immunology 10/2010; 126(4):736-7. DOI:10.1016/j.jaci.2010.07.040 · 11.25 Impact Factor
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ABSTRACT: Last year's "Advances in pediatric asthma" concluded with the following statement: "If we can close these [remaining] gaps through better communication, improvements in the health care system and new insights into treatment, we will move closer to better methods to intervene early in the course of the disease and induce clinical remission as quickly as possible in most children." This year's summary will focus on recent advances in pediatric asthma that take steps moving forward as reported in Journal of Allergy and Clinical Immunology publications in 2010. Some of these recent reports show us how to improve asthma management through steps to better understand the natural history of asthma, individualize asthma care, reduce asthma exacerbations, and manage inner-city asthma and some potential new ways to use available medications to improve asthma control. It is clear that we have made many significant gains in managing asthma in children, but we have a ways to go to prevent asthma exacerbations, alter the natural history of the disease, and reduce health disparities in asthma care. Perhaps new directions in personalized medicine and improved health care access and communication will help maintain steady progress in alleviating the burden of this disease in children, especially young children.The Journal of allergy and clinical immunology 01/2011; 127(1):102-15. DOI:10.1016/j.jaci.2010.11.018 · 11.25 Impact Factor
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ABSTRACT: The immunologic reaction to fungal stimuli has long been thought to be a contributor to the development of sinonasal disease. We aim to review the role of fungi in upper and lower airway inflammatory diseases. The immune response to fungi in the pathogenicity of specific respiratory inflammatory diseases such as allergic bronchopulmonary aspergillosis and a subtype of CRS known as allergic fungal rhinosinusitis has been relatively well described. Fungi are thought to serve both as immunogenic antigens and as adjuncts to inflammation through protease activity. Development of a recent murine mouse model of asthma bypassing the pre-sensitization of allergen further suggests a broader role for fungi in allergic asthma. The literature is lacking in defining a clear presence of fungi within the inflamed sinus cavity of CRS patients and its potential immunologic effects, as well as the utility of antifungal therapy for CRS management. We will review these data and potential common molecular mechanisms activated by fungi in the common pathway toward upper and lower airway inflammatory pathology.Immunological Investigations 01/2011; 40(7-8):767-85. DOI:10.3109/08820139.2011.596876 · 1.90 Impact Factor