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Inflammatory cell distribution within and along asthmatic airways.

Pulmonary and Critical Care Division, Departments of Medicine and Departments of Surgery and Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 08/1998; 158(2):565-72. DOI: 10.1164/ajrccm.158.2.9705036
Source: PubMed

ABSTRACT Asthmatic airways are infiltrated with inflammatory cells that release mediators and cytokines into the microenvironment. In this study, we evaluated the distribution of CD45-positive leukocytes and eosinophils in lung tissue from five patients who died with severe asthma compared with five patients with cystic fibrosis. For morphometric analysis, the airway wall was partitioned into an "inner" area (between basement membrane and smooth muscle) and an "outer" area (between smooth muscle and alveolar attachments). Large airways (with a perimeter greater than 3.0 mm) from patients with asthma or cystic fibrosis had a greater density of CD45-positive cells (p < 0.05) and eosinophils (p < 0.001) in the inner airway region compared with the same airway region in small airways. Furthermore, in small airways, asthmatic lungs showed a greater density of CD45-positive cells (p < 0.01) and eosinophils (p < 0.01) in the outer compared with the inner airway wall region. These observations indicate that there are regional variations in inflammatory cell distribution within the airway wall in patients with asthma that are not observed in airways from patients with cystic fibrosis. We speculate that this inflammatory cell density in peripheral airways in severe asthma may relate to the peripheral airway obstruction characteristic of this condition.

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    • "epithelium versus interstitium ). In another report, comparative analysis of patients with severe asthma and cystic fibrosis has indicated that the distribution of CD45+ cells and eosinophils within mucosal and submucosal compartments of large versus small airways is variable in disease-specific manner (Haley et al., 1998). It is apparent from these studies that definition of compartments and airway generations for immune cells can define a pathological process in the lung. "
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    ABSTRACT: Airway inflammation is a key feature of bronchial asthma. In asthma management, according to international guidelines, the gold standard is anti-inflammatory treatment. Currently, only conventional procedures (i.e., symptoms, use of rescue medication, PEF-variability, and lung function tests) were used to both diagnose and evaluate the results of treatment with anti-inflammatory drugs. New methods for evaluation of degree of airway inflammation are required. Nitric oxide (NO) is a gas which is produced in the airways of healthy subjects and especially produced in asthmatic airways. Measurement of NO from the airways is possible, and NO can be measured from exhaled air. Fractional exhaled NO (FENO) is increased in asthma, and the highest concentrations are measured in asthmatic patients not treated with inhaled corticosteroids (ICS). Steroid-treated patients with asthma had levels of FENO similar to those of healthy controls. Atopic asthmatics had higher levels of FENO than did nonatopic asthmatics, indicating that level of atopy affected FENO level. Associations between FENO and bronchial hyperresponsiveness (BHR) occur in asthma. The present study demonstrated that measurement of FENO had good reproducibility, and the FENO variability was reasonable both short- and long-term in both healthy subjects and patients with respiratory symptoms or asthma. We demonstrated the upper normal limit for healthy subjects, which was 12 ppb calculated from two different healthy study populations. We showed that patients with respiratory symptoms who did not fulfil the diagnostic criteria of asthma had FENO values significantly higher than in healthy subjects, but significantly lower than in asthma patients. These findings suggest that BHR to histamine is a sensitive indicator of the effect of ICS and a valuable tool for adjustment of corticosteroid treatment in mild asthma. The findings further suggest that intermittent treatment periods of a few weeks’ duration are insufficient to provide long-term control of BHR in patients with mild persistent asthma. Moreover, during the treatment with ICS changes in BHR and changes in FENO were associated. FENO level was associated with BHR measured by a direct (histamine challenge) or indirect method (exercise challenge) in steroid-naïve symptomatic, non-smoking asthmatics. Although these associations could be found only in atopics, FENO level in nonatopic asthma was also increased. It can thus be concluded that assessment of airway inflammation by measuring FENO can be useful for clinical purposes. The methodology of FENO measurements is now validated. Especially in those patients with respiratory symptoms who did not fulfil the diagnostic criteria of asthma, FENO measurement can aid in treatment decisions. Serial measurement of FENO during treatment with ICS can be a complementary or an alternative method for evaluation in patients with asthma. Astma on tulehdus keuhkoputkien limakalvolla ja inhaloitava kortikosteroidi (ICS)on hoidon kulmakivi. Jos astman seurantaan käytetään vain spirometriaa, PEF-seurantaa, oirekyselyä sekä avaavan lääkkeen tarvetta, ei astmaan liittyvä tulehdusta pystytä arvioimaan. Siis kaivataan uusia menetelmiä, joilla voidaan mitata myös astmaan liittyvä tulehdus. Uloshengitysilman typpioksidin (FENO) määrä on lisääntynyt astmassa ja ICS-hoidetuilla potilailla FENO on samaa luokkaa kuin terveillä. Kuitenkin, atooppisten astmaatikkojen arvot ovat selvästi korkeammat ja näin ollen atopian merkitys FENO-pitoisuuteen on tärkeä. Kirjallisuuden perusteella FENO ja keuhkoputkien supistumisherkkyys (BHR) assosioituvat vaihtelevasti. Tutkimus koostui viidestä osatyöstä, joissa kahdessa keskityttiin metodologisiin tekijöihin. FENO-mittauksen toistettavuus on hyvä terveillä ja mahdollista astmaa sairastavilla sekä lyhyellä että pitkällä aikavälillä. FENO-pitoisuuden normaaliarvon yläraja oli 12 ppb. FENO-pitoisuus oli korkeampi mahdollista astmaa sairastavilla kuin terveillä, mutta matalampi kuin astmaa sairastavilla. Tutkimus osoitti, että BHR on herkkä mittari osoittamaan hengitettävän flutikasonihoidon vaikutusta 26 astmaatikolla. Lisäksi, tulos viittaa siihen, että muutaman viikon hoito ICS:lla on riittämätön pitkällä aikavälillä. Kahden viikon ICS-hoidon jälkeen nähtiin merkittävä assosiaatio FENO-tason vähenemisessä ja BHR-tason paranemisessa. 181 potilaalla, joilla epäiltiin astmaa, FENO ja BHR mitattuna sekä rasitusastmareaktiolla että histamiinialtistuksella korreloivat vain atoopikoilla. Lisäksi, tutkimus osoitti, että FENO-taso oli korkeampi ei-atooppista astmaa sairastavilla kuin terveillä ja matalampi kuin atooppista astmaa sairastavilla. Kun atooppinen astma jaettiin vähän ja paljon herkistyneisiin potilaisiin, niin tulosten perusteella voitiin osoittaa, että ei-atooppisten ja vähän herkistyneiden astmaatikkojen FENO-taso sekä BHR mitattuna sekä rasitusastmareaktiolla että histamiinialtistuksella ovat samanlaisia. Tulokset viittaavat siihen, että astmaan liittyvää tulehdusta kannattaa tutkia FENO-mittauksella myös kliinisessä tarkoituksessa. Metodologia on nyt validoitu. Kun epäillään astmaa, FENO-mittaus voi auttaa kliinisessä päätöksenteossa. Toistuvat FENO-mittaukset ICS-hoidon aikana voivat olla täydentävä tai vaihtoehtoinen menetelmä astman hoidossa.
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