Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

IntroductionCrohn's disease [CD] is a chronic inflammatory bowel disease [IBD] that can result in progressive bowel damage and disability 1 . CD can affect individuals of any age, from children to the elderly, 2,3 and may cause significant morbidity and impact on quality of life. Up to one-third of patients present with complicated behaviour [strictures, fistula, or abscesses] at diagnosis 4 . Most patients over time will develop a complication, with roughly 50% of patients requiring surgery within 10 years of diagnosis [5][6][7] . As the precise aetiology of CD remains unknown, a curative therapy is not yet available 8 . Several agents are available for the medical treatment of CD. Medical agents include mesalazine [5-ASA], locally active steroids [such as budesonide], systemic steroids, thiopurines such as azathioprine [AZA] and mercaptopurine [MP], methotrexate [MTX], and biological therapies [such as anti-TNF, anti-integrins, and anti-IL12/23].The European Crohn's and Colitis Organisation [ECCO] produces and regularly updates several guidelines aimed at providing evidence-based guidance on critical aspects of IBD care to all healthcare professionals who manage patients with IBD. To provide high-quality evidence-based recommendations on medical and surgical treatment in CD, ECCO decided to develop these guidelines by adopting the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] approach 9 . GRADE is a systematic process for developing guidelines that addresses how to frame the healthcare questions, summarize the evidence, formulate the recommendations, and grade their strength and the quality of the associated evidence. GRADE increases transparency at all levels of this process and makes explicit the three considerations that lead to a particular recommendation: the quality of the evidence, the balance of benefits and harms, and the patients' values and preferences. Therefore, ECCO reviewed the available high-quality evidence on the medical management of CD and developed evidence-based recommendations on the medical treatment of adult patients with CD. These guidelines do not cover specific situations, such as post-operative management of adult patients with CD, which was already covered in the last ECCO Guidelines on Crohn's disease 10 . MethodsBased on the GRADE workflow, the Guidelines Committee of ECCO [GuiCom] selected a panel of 48 experts supported by a team of methodologists and librarians. Selection was based on IBD expertise, scientific background, and knowledge of the GRADE methodology. All panellists received adequate training in GRADE before starting the process.Additionally, four patients with CD representing the European Federation of Crohn's and Colitis Associations [EFCCA] were invited to participate in all face-to-face meetings and to provide their experiences and state their preferences.Three domains for medical treatment of CD were identified: 1) induction therapy 2) maintenance therapy 3) therapy of fistulizing perianal disease.All panellists were assigned to...

SllmmsLryEosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, "eotaxin," exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-loe, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-lcr, and MCP-1 were all inactive in inducing ~11In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with P.ANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung.

SummaryExperiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B 4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.

This article is the second in a series of two publications relating to the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn’s disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn’s disease and an update of previous guidelines.