Extracorporeal Carbon Dioxide Removal in the Treatment of Status Asthmaticus.

OBJECTIVES: Venovenous extracorporeal carbon dioxide removal may be lifesaving in the setting of status asthmaticus. DESIGN: Retrospective review. SETTING: Medical ICU. PATIENTS: Twenty-six adult patients with status asthmaticus treated with venovenous extracorporeal carbon dioxide removal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data and characteristics of current and prior asthma treatments were obtained from the electronic medical record. Mechanical ventilator settings, arterial blood gases, vital signs, and use of vasopressors were collected from the closest time prior to cannulation and 24 hours after initiation of extracorporeal carbon dioxide removal. Extracorporeal carbon dioxide removal settings, including blood flow and sweep gas flow, were collected at 24 hours after initiation of extracorporeal carbon dioxide removal. Outcome measures included rates of survival to hospital discharge, ICU and hospital lengths of stay, duration of invasive mechanical ventilation and extracorporeal carbon dioxide removal support, and complications during extracorporeal carbon dioxide removal. Following the initiation of extracorporeal carbon dioxide removal, blood gas values were significantly improved at 24 hours, as were peak airway pressures, intrinsic positive end-expiratory pressure, and use of vasopressors. Survival to hospital discharge was 100%. Twenty patients (76.9%) were successfully extubated while receiving extracorporeal carbon dioxide removal support; none required reintubation. The most common complication was cannula-associated deep venous thrombosis (six patients, 23.1%). Four patients (15.4%) experienced bleeding that required a transfusion of packed RBCs. CONCLUSIONS: In the largest series to date, use of venovenous extracorporeal carbon dioxide removal in patients with status asthmaticus can provide a lifesaving means of support until the resolution of the exacerbation, with an acceptably low rate of complications. Early extubation in select patients receiving extracorporeal carbon dioxide removal is safe and feasible and avoids the deleterious effects of positive-pressure mechanical ventilation in this patient population.

[Sudden death during sport activity in Tunisia: autopsy study in 32 cases]. / La mort subite au cours d'une activité sportive en Tunisie : à propos d'une série autopsique de 32 cas.

PURPOSE: To develop profile of the victims and to study circumstances, causes of death and autopsy findings. METHODS: Retrospective study of cases of sudden death in sport activity whose autopsy was performed in forensic department of Tunis, between January 2005 and December 2009. RESULTS: During study period, 32 cases of SD in sport activity were recorded. These are amateur athletes predominantly male (84% of cases). Victims are aged between 15 and 79 years with an average age of about 33.16 years. Young subjects whose age is less than 35 years representing 68.7% of cases. 9.3% of victims had a family history of SD and 18.7% of cases had a known cardiac history. The sports most involved are running (40.6% of cases), football (31.3% of cases) and dance (12.5% of cases). Sixty-nine percent of victims died during sports activities. Presence of witnesses was noted in all cases; however, none of these witnesses has begun resuscitation. Cause of death was cardiac in 84.4% of cases. In young athletes, hypertrophic cardiomyopathy is the leading cause (nine cases), followed by arrhythmogenic right ventricular dysplasia (three cases). Among other causes, there is the myocardial bridge, congenital anomalies of the coronary arteries, aortic dissection and dilated cardiomyopathy. Beyond 35 years, coronary artery diseases represent the cause of death (nine cases). Only case of death secondary to non-cardiac disease occurred after a severe asthma attack. In four cases (12.5%), no cause of death was identified after a complete autopsy accompanied by further investigations. The cause of the death was imputed to a rhythmic pathology. CONCLUSION: This is the first study dealing with autopsy in SD in sport have provided a specific profile of victims. Other studies on larger samples and using standardized autopsy protocols are needed.

Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma.

BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods. RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found. CONCLUSION: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.

[Predictive factors associated with severity of asthma exacerbations]. / Astim ataklarinda agirligi belirleyici risk faktörleri.

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Abnormalities of the bronchial arteries in asthma.

STUDY OBJECTIVES: The bronchial arteries supply systemic blood to the airways, tracheobronchial lymph nodes, and nerves. Their structure has not been studied in patients with asthma. DESIGN: Case-control study of pathologic changes of bronchial arteries in asthma. PARTICIPANTS AND METHODS: Postmortem lungs were examined from three case groups: (1) fatal asthma (n = 12), death due to asthma; (2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes; and (3) nonasthmatic control subjects (n = 12), no history of asthma and death due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1 to 1.0 mm, the areas of lumen, intima, and media were measured and compared between case groups. RESULTS: There were no significant differences in artery size (outer diameter) or in medial area between the three groups. In the two asthma groups, the intimal area was increased (p < 0.05), with a corresponding decrease in luminal area compared with the control group. There was a significant effect of gender, age, and smoking on intimal area. In the asthma cases, the area of bronchial artery intima was related to duration of asthma (p < 0.05), and this increase was associated with smooth muscle proliferation, reduplication, and calcification of the elastica, but not with inflammatory cell infiltration. CONCLUSIONS: While the pathophysiologic significance of these changes is uncertain, the relation to duration of asthma, age, and smoking suggests a secondary response to chronic airway disease.

Airway proteoglycans are differentially altered in fatal asthma.

It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter < or =6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (microm2)/epithelial basement membrane length (microm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 microm, C = 3.97 +/- 1.17 microm, p = 0.042; lumican: A = 1.97 +/- 0.37 microm, C = 5.66 +/- 0.99 microm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 +/- 0.84 microm, C = 5.16 +/- 0.61 microm, p = 0.045; large: A = 18.38 +/- 1.94 microm, C = 11.90 +/- 2.86 microm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma.

Inflammatory cell mapping of the respiratory tract in fatal asthma.

BACKGROUND: The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. OBJECTIVE: We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. METHODS: Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. RESULTS: Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). CONCLUSION: Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.

[Revision of the 3rd Consensus Conference in Intensive Care and Emergency Medicine in 1988: management of acute asthmatic crisis in adults and chidren (excluding infants)]. / Révision de la troisième conférence de consensus en réanimation et médecine d'Urgence de 1988: prise en charge des crises d'asthme aiguës graves de l'adulte et de l'enfant (à l'exclusion du nourrisson).

Experts designated by the "référentiels" committee of the SRLF analyzed the numerous articles published after the French consensus conference on the severe acute asthma of 1988. From their work, a revision of this consensus conference has been performed. The pediatric specificity has been added in this revision. There is no severity score able to predict the severity of acute asthma on admission. In every case, the nebulization of beta-2 agonists represents the priority treatment. The nebulization of anticholinergic associated with the beta-2 agonists induces a moderate additional effect. In the absence of response to nebulizations, the usefulness of the beta-2 agonists associated intravenous. Administration is not demonstrated. Corticosteroids should be administered using a 1 to 2 mg per kg dosage, but their efficacy is delayed. In adult patients, aminophylline should not be prescribe, but it is still used by some pediatricians. Other associated treatments (adrenaline, magnesium sulfate, helium-oxygen mixture) did not demonstrate their efficacy as adjunctive therapies. The therapeutic response should be evaluated using the peak flow determination.

[Pathomorphological alterations in the hypothalamo-hypophyseal-adrenal system in bronchial asthma patients died in status asthmaticus]. / Patomorfologicheskie izmeneniia gipotalamo-gipofizarno-nadpochechnikovoi sistemy u bol'nykh bronkhial'noi astmoi, pogibshikh v astmaticheskom statuse.

Morphologic changes in the paraventricular nucleus (PVN) of the hypothalamus, in hypophyseal frontal lobe and adrenal cortex are adaptive and reactive changes. In status asthmaticus, there is a high hormonal activity manifesting morphologically with hypertrophic neurosecretory granules.

Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma: characterization of pathways available to eosinophils for generating reactive nitrogen species.

Eosinophil recruitment and enhanced production of NO are characteristic features of asthma. However, neither the ability of eosinophils to generate NO-derived oxidants nor their role in nitration of targets during asthma is established. Using gas chromatography-mass spectrometry we demonstrate a 10-fold increase in 3-nitrotyrosine (NO(2)Y) content, a global marker of protein modification by reactive nitrogen species, in proteins recovered from bronchoalveolar lavage of severe asthmatic patients (480 +/- 198 micromol/mol tyrosine; n = 11) compared with nonasthmatic subjects (52.5 +/- 40.7 micromol/mol tyrosine; n = 12). Parallel gas chromatography-mass spectrometry analyses of bronchoalveolar lavage proteins for 3-bromotyrosine (BrY) and 3-chlorotyrosine (ClY), selective markers of eosinophil peroxidase (EPO)- and myeloperoxidase-catalyzed oxidation, respectively, demonstrated a dramatic preferential formation of BrY in asthmatic (1093 +/- 457 micromol BrY/mol tyrosine; 161 +/- 88 micromol ClY/mol tyrosine; n = 11 each) compared with nonasthmatic subjects (13 +/- 14.5 micromol BrY/mol tyrosine; 65 +/- 69 micromol ClY/mol tyrosine; n = 12 each). Bronchial tissue from individuals who died of asthma demonstrated the most intense anti-NO(2)Y immunostaining in epitopes that colocalized with eosinophils. Although eosinophils from normal subjects failed to generate detectable levels of NO, NO(2-), NO(3-), or NO(2)Y, tyrosine nitration was promoted by eosinophils activated either in the presence of physiological levels of NO(2-) or an exogenous NO source. At low, but not high (e.g., >2 microM/min), rates of NO flux, EPO inhibitors and catalase markedly attenuated aromatic nitration. These results identify eosinophils as a major source of oxidants during asthma. They also demonstrate that eosinophils use distinct mechanisms for generating NO-derived oxidants and identify EPO as an enzymatic source of nitrating intermediates in eosinophils.

Respiratory effects of halothane in a patient with refractory status asthmaticus.

We describe the case of a 36 year old patient who was admitted to the intensive care unit (ICU) for an acute asthma attack that failed to respond to conventional treatment and required mechanical ventilation. The patient's condition improved after halothane was administered; treatment with this inhalational anaesthetic lasted 7 h, and the beneficial effect was obtained by employing concentrations between 0.5 and 2%. Under constant mechanical ventilator settings, a highly significant linear correlation between peak airway pressure and arterial pCO(2)(r: 0.98 P<0.001) was observed. The decrease in p(a)CO(2)induced by halothane may be explained by the diminished dead space that results from the drop in peak airway pressure. Arterial hypotension, which improved with inotropic agents, was the only complication that seemed related to the inhaled anaesthetic. The patient was extubated 24 h after her arrival to the ICU and discharged 72 h later. A causal relationship between the administration of halothane and clinical improvement is suggested.

Clinical features and outcome of management of severe acute asthma (status asthmaticus) in the intensive care unit of a tertiary medical center.

AIM OF THE STUDY: The recognition and management of severe acute asthma have attracted considerable attention since the seventies because of the morbidity and mortality that may accompany the condition. Recognition and appropriate management of severe acute asthma is essential. Admission to intensive care, intubation and ventilation risks versus benefit have been argued. We highlight these controversies by documenting our experience and comparing it to others in the literature METHODOLOGY: We prospectively document our experience over a two-year period in the management of severe asthma in the intensive Care Unit (ICU). Patients were established asthmatics, who came in severe exacerbation. Attention was paid to the duration of onset of acute attack, time to presentation, spirometric and blood gas data, the type of treatment given, factors responsible for complications and mortality were identified. The findings in this study were compared with those in similar studies in the literature. RESULTS: A total of 30 patients were studied. Twenty-one patients were ventilated and 9 were not. 82% had a history of asthma longer than 5 years. The duration of symptoms before admission to ICU was very short (one day or less in 57%). Hypercapnia was significantly higher in intubated patients. The duration of stay in ICU and hospital was longer for intubated patients (P<0.02). Complications were higher in intubated patients. CONCLUSION: ICU care provides an excellent setting for management of acute severe asthma. The reported high morbidity and mortality in ICU can be improved. Without ICU care the mortality and morbidity increases,so physicians should not hesitate to admit asthmatics early to ICU.

[Management of severe acute asthma in children in pediatric urgent and intensive care units]. / Prise en charge de l'asthme aigu sévère de l'enfant en unité de soins d'urgence et de soins intensifs pédiatriques.

Mortality in cases of severe asthma attacks in children is evaluated at 1%. During initial medical care, repeated evaluation of clinical and para-clinical severity criteria constitutes the main therapeutic guide. Emergency care treatment is based mainly on oxygen therapy, bronchodilatory therapy by discontinuous inhalation, and general corticotherapy. Intravenous theophylline treatment is controversial. The response after a few hours should allow a decision to be made [1] to follow up with outpatient treatment (rapid marked improvement), [2] to continue the hospital treatment (stabilization), or [3] to transfer to intensive care (worsening, exhaustion). In the intensive care unit, the treatment is based on continuous intravenous administration of beta 2 mimetics in addition to the above therapies. The objective is to avoid resorting to assisted ventilation. When this proves necessary, it must not be detrimental; controlled alveolar hypoventilation allows dynamic hyper-inflation linked to ventilation to be reduced. Prevention of relapse is indispensable. This requires hospitalization in a specialized care unit after discharge from intensive care.

Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus.

In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA, together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5 micrograms gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; in addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change in ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.

Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus.

Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF-alpha, and of the active form of TGF-beta1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1beta was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1beta (79% inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies).

Impaired perception of dyspnea in patients with severe asthma. Relation to sputum eosinophils.

Poor dyspnea perception might be a risk factor for developing asthma exacerbations. We investigated whether severe asthmatics with recurrent exacerbations (brittle asthma) have different dyspnea perception and sputum cells compared with equally severe, but stable asthmatics, or patients with mild steroid-naive asthma. Fifteen brittle asthmatics (13 female, median age 28 yr [range, 20 to 47 yr]), 15 matched severe-stable asthmatics (14 female, median age 26 yr [range, 17 to 52 yr]), and 11 mild asthmatics (8 female, median age 25 yr [range, 19 to 43 yr]) underwent inhalation tests with methacholine (MCh), and hypertonic saline combined with sputum induction. Dyspnea was assessed by Borg and Visual Analogue Scale (VAS), plotted against the percent fall in FEV1, and expressed as the slope of the regression line (Slope-Borg and Slope-VAS). The brittle and stable asthmatics had poorer perception than patients with mild asthma (Slope-Borg [p = 0.036], Slope-VAS [p < 0.001] for MCh). In patients with brittle asthma the perception was less as compared with severe-stable asthma (Slope-Borg for MCh: p = 0.05). In the severe asthmatics there was an inverse correlation between sputum eosinophilia and Slope-Borg and Slope-VAS (R = -0.55, p = 0. 002 and R = -0.37, p = 0.049), whereas this correlation was a positive one in the mild asthmatics (R = 0.79, p = 0.012 and R = 0. 67, p = 0.05). In conclusion, patients with severe asthma, particularly those with recurrent exacerbations, have blunted perception of dyspnea, which is related to the degree of sputum eosinophilia. This suggests that increased sputum eosinophilia is an indicator of clinical instabililty, and that eosinophilic airways inflammation might affect dyspnea perception in severe asthma.

Bronchial neutrophilia in patients with noninfectious 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.