interleukin-8 and Status-Asthmaticus

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.

Topics: Adult; Aged; Blood Proteins; Bronchi; Bronchoalveolar Lavage Fluid; Eosinophil Granule Proteins; Female; Histamine; Humans; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Neutrophils; Respiration, Artificial; Respiratory Insufficiency; Respiratory Tract Infections; Ribonucleases; Status Asthmaticus

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.

Topics: Acute Disease; Adenoviridae; Adult; Asthma; Blood Proteins; Common Cold; Coronavirus; Eosinophil Granule Proteins; Eosinophils; Feasibility Studies; Female; Fibrinogen; Humans; Inflammation; Inflammation Mediators; Influenza A virus; Influenza B virus; Influenza, Human; Interferon-gamma; Interleukin-2; Interleukin-5; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Respiratory Syncytial Viruses; Rhinovirus; Ribonucleases; Sputum; Status Asthmaticus

Peripheral blood mononuclear cells (PBMC) isolated from patients with acute severe asthma on the day of admission to hospital were cultured in vitro in serum-free medium in the absence of mitogenic stimulants for as long as 72 h. PBMC isolated from control groups (mild asthma, chronic obstructive airway disease, normal subjects) were cultured in a similar fashion. After incubation, the culture supernatants were tested for neutrophil chemotactic activity (NCA) using a modified Boyden chamber technique. PBMC from patients with acute severe asthma elaborated significantly greater amounts of NCA into the culture supernatants as compared with all three control groups (p less than 0.01). The amounts of PBMC-derived NCA from the same patients after 7 days of hospital therapy and clinical improvement were reduced (p less than 0.01). A correlation was observed between the extent of reduction in spontaneous release of NCA by PBMC derived from patients with acute severe asthma and the degree of clinical improvement of their asthma (p less than 0.02). Both monocytes and lymphocytes, when cultured separately, released NCA in amounts sufficient to account for the total activity released by unfractionated PBMC. NCA in PBMC culture supernatants accumulated progressively with time, a process inhibited in a dose-dependent fashion by cycloheximide. The amounts of NCA in culture supernatants did not correlate with the concentrations of histamine in lysates of the PBMC prepared just prior to culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Cells, Cultured; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, Gel; Humans; Interleukin-8; Leukocytes, Mononuclear; Middle Aged; Neutrophils; Status Asthmaticus