Inflammatory reactions in the airways are thought to play an important role in asthma pathogenesis. The goal of this work was to test prospectively the hypothesis that the pulmonary inflammatory response to segmental antigen challenge is greater in allergic asthmatic (AA) subjects than in allergic nonasthmatic (ANA) subjects. A total of 46 ragweed-allergic subjects, 27 AA and 19 ANA, took part in these studies. Subjects had normal or nearly normal pulmonary function, were on no chronic medication, and were characterized as to their skin sensitivity to intradermal ragweed injection, their nonspecific responsiveness to methacholine, and the presence (or absence) of a late asthmatic response after whole-lung antigen challenge. Subjects then underwent bronchoscopy, bronchoalveolar lavage (BAL) of a control lung segment, antigen lung challenge of a contralateral lung segment with 5 ml of a concentration of ragweed solution 100-fold higher than that required to produce a positive skin reaction, and finally, BAL of the challenged segment after 24 h. AA did not differ from ANA in any inflammatory parameter measured in BAL fluid (total cells/ml, macrophages/ml, lymphocytes/ml, eosinophils/ml, neutrophils/ml, total protein, albumin, urea, or eosinophil cationic protein) 24 h after challenge. In addition, there was no relationship between nonspecific bronchial responsiveness to methacholine and eosinophils recruited to the lung by segmental antigen challenge. Rather, in both groups a marked inflammatory response was seen only in the subgroup of subjects who demonstrated a late airway reaction after whole-lung antigen challenge, regardless of disease classification.(ABSTRACT TRUNCATED AT 250 WORDS)

Proactive use of a bowel management device appears to reduce some infectious sequelae in a complicated burn care population and proved cost-effective for our facility.

Evidence from in vitro studies suggests a potential role for vascular cell adhesion molecule-1 (VCAM-1) in eosinophil trafficking. We hypothesized that induction of VCAM-1 occurs in the lung during IgE-mediated airway inflammation in humans. The technique of segmental antigen provocation followed by bronchoalveolar lavage (BAL) at 24 h was used to study 27 ragweed-allergic asthmatics (AA) and 18 atopic nonasthmatics (ANA). Total and differential cell counts were performed, and IL-4, IL-5, and soluble (VCAM) (sVCAM) levels in concentrated BAL fluid were measured by ELISA. A large increase in sVCAM levels after segmental challenge in both AA and ANA (1.79 +/- 0.31 to 139.39 +/- 68.58 ng/ml, p < 0.0005 and 2.85 +/- 0.80 to 98.25 +/- 77.35 ng/ml, p < 0.05, respectively) was observed. BAL IL-4 and IL-5 also increased after challenge (IL-4: 51.7 +/- 17.72 to 150.1 +/- 58.82 pg/ml, 0.05 < p < 0.10, n = 20 for AA, and 36.6 +/- 9.05 to 116.8 +/- 51.5 pg/ml, 0.05 < p < 0.10, n = 15 for ANA; IL-5: 0 to 2.67 +/- 1.62 ng/ml, p < 0.01, n = 16 for AA, and 0 to 2.87 +/- 2.16 ng/ml, 0.05 < p < 0.10, n = 10 for ANA). In both groups, the majority of the increase in sVCAM, IL-4, and IL-5 was accounted for by subjects who displayed a dual phase response after whole-lung antigen inhalation. This fact, plus the strong correlation observed between postchallenge sVCAM, IL-4, and IL-5 levels and eosinophil influx, suggests that VCAM, IL-4, and IL-5 play important roles in the recruitment of eosinophils to the lung of humans after antigen challenge.

Events occurring up to 16 d after antigen challenge were characterized using a novel protocol employing four bronchoscopies, two segmental antigen challenge (SAC) procedures (on Days 1 and 2), and six bronchoalveolar lavages (BALs) (on Days 1, 2, 9, and 16) in three groups: ragweed allergic asthmatics with dual phase airway reactions (AA-D), allergic asthmatics with a single early airway reaction (AA-S), and nonallergic nonasthmatic control subjects. In AA-D subjects, SAC produced a marked eosinophilic inflammatory response at 24 h associated with eosinophil degranulation (eosinophil cationic protein [ECP] in BAL fluid) and lung injury, which largely resolved by Day 16. When the second antigen-challenged segment (SAC performed on Day 2) was lavaged 7 d after challenge (Day 9), a persistent pulmonary eosinophilia was noted accompanied by minimal elevations in ECP and albumin. Eosinophil-active cytokines showed unique patterns: interleukin-5 (IL-5) increased in the antigen segment on Day 2 then returned to baseline after 7 d; granulocyte-macrophage colony-stimulating factor (GM-CSF) peaked at Day 2 but was persistently elevated throughout Day 16 in antigen segments, and increased in control segments at late time points; IL-3 levels were constant and similar in antigen and control segments. Changes were specific to AA-D subjects in comparison with control subjects. Elements of the IgE-mediated pulmonary inflammatory response differ markedly in their development and resolution.

Inflammation in allergic individuals is hypothesized to elevate stress proteins [heat shock proteins (HSP)] in airway epithelium, which may protect cells from further adverse conditions. Allergic, either asthmatic or not, and normal volunteers participated in a 2-day segmental allergen challenge bronchoscopic procedure. Bronchial epithelium was obtained before and after challenge. Epithelium was exposed to medium with H2SO4 (pH5), returned to medium at pH 7.4, and finally harvested for Western blotting with anti-27-kDa HSP (HSP27) antibody. Prechallenge epithelium of all subjects had significantly inhibited ciliary function by H2SO4 (pH 5) conditions (P < 0.001); only epithelium of normals recovered (P = 0.02). Allergic subjects with mild inflammation (< 50 micrograms/ml increase in albumin in bronchoalveolar lavage) had significantly increased HSP27 postchallenge (P = 0.01) and little ciliary dysfunction at pH 5, whereas subjects with severe inflammation (> 50 micrograms/ml increase in albumin) had little change in HSP27 and significant ciliary inhibition (P = 0.02). Normal epithelium had similar trends in HSP27 and equivalent inhibition of ciliary activity at pH 5 before and after allergen challenge. These data indicate that mild inflammation to allergen elevates HSP27 stress protein levels, thereby potentially protecting epithelial function from additional adverse conditions.