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This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.

Resume La bronchopneumopathie chronique obstructive (BPCO) est causee a plus de 90 % par le tabagisme, mais plusieurs autres facteurs de risque ont ete clairement identifies ; la pollution exterieure (atmospherique) en fait partie, mais son implication dans la constitution de la maladie est tres difficile a demontrer. Ses effets sur la fonction respiratoire ne sont reellement etudies que depuis une vingtaine d’annees grâce a des etudes de cohortes, longues et fastidieuses, ce qui explique les controverses concernant leurs conclusions et les difficultes a mettre en evidence des resultats statistiquement significatifs. Ces difficultes sont d’autant plus grandes que la pollution est faite d’un ensemble de molecules (gaz, particules…), et qu’il faut rechercher l’effet respiratoire de chaque constituant au sein d’une population donnee. Par ailleurs, mettre en evidence un lien de causalite entre pollution atmospherique et BPCO necessite d’analyser ses effets a court terme, a long terme, ses effets physiologiques, toxicologiques et cliniques, depuis l’enfance jusqu’a l’âge adulte. Il semble qu’a l’heure actuelle, de nombreux travaux soient concordants et stigmatisent certains polluants exterieurs comme responsables d’alteration de la fonction respiratoire, notamment via le stress oxydatif. Neanmoins, d’autres resultats sont attendus pour confirmer l’implication exacte de chaque composant, ce qui va probablement devenir un enjeu majeur de sante publique. Le but de ces analyses est d’identifier les populations a risque, afin de proposer des actions preventives, des seuils de tolerance, pour eviter la constitution d’une BPCO invalidante.

Exacerbations of COPD are common and cause a considerable burden to the patient and the healthcare system. To optimize the hospital care of patients with exacerbations of COPD, clinicians should be aware of some key points: management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define those patients requiring hospital admission and those who could be managed as outpatients. In hospitalized patients, the appropriate level of care should be determined by the initial severity and response to initial medical treatment. Medical treatment should follow recent recommendations, including rest, titrated oxygen therapy, inhaled or nebulized short-acting bronchodilators (Beta2-agonists and anticholinergic agents), DVT prevention with LMWH, steroids in most severely ill patients, unless there are contraindications and antibiotics in the case of a clear bacterial infectious aetiology. Severe exacerbations may lead to acute hypercapnic respiratory failure. Unless contraindicated, non-invasive ventilation (NIV) should be the first line ventilatory support for these patients. NIV should be commenced early, before severe acidosis ensues, to avoid the need for endotracheal intubation and to reduce mortality and treatment failures. Several randomised controlled clinical trials support the use of NIV in the management of acute exacerbations of COPD, demonstrating a decreased need for mechanical ventilation and an improved survival. In most severe cases, NIV should be provided in ICU. Although it has been shown that for less severe patients (with pH values>7.30), NIV can be administered safely and effectively on general medical wards, a lead respiratory consultant and trained nurses are mandatory. Mechanical ventilation through an endotracheal tube should be considered when patients have contraindications to the use of NIV or fail to improve on NIV. The duration of mechanical ventilation should be shortened as much as possible by an early weaning process, including preventive post-extubation NIV in hypercapnic patients. hospital stay could be shortened by non-invasive treatments. Future exacerbations should be avoided by respiratory specialist management of the patients, including education, optimization of long-term medical treatment, vaccinations, nutritional support, and pulmonary rehabilitation.

A 60 year old male patient was admitted to hospital with pulmonary and cerebral abscesses. A percutaneous lung biopsy under CT scanning showed actinomycosis. After 4 weeks antibiotic therapy with ceftriaxone and metronidazole there was an improvement in the pulmonary lesion but new cerebral lesions appeared. A neurosurgical cerebral biopsy showed evidence of metastatic squamous carcinoma, probably of pulmonary origin. The diagnosis had been delayed by the presence of the actinomycosis. His general condition did not permit anti-tumour treatment and the patient soon afterwards. In the presence of pulmonary actinomycosis an associated malignancy should be excluded.

Un homme de 61 ans a ete pris en charge pour un cancer bronchique dissemine, revele par une thrombose veineuse profonde. L’evolution s’est compliquee d’une thrombose arterielle conduisant a l’amputation, puis d’une progression tumorale tres rapide conduisant au deces en quelques semaines. Si l’association entre thromboses veineuses et cancer est bien connue, le lien avec les phenomenes thrombotiques arteriels l’est moins. Cette observation est l’occasion d’en discuter les aspects physiopathologiques, cliniques et evolutifs, ainsi que leurs implications pour la prise en charge.

Introduction La bronchopneumopathie chronique obstructive (BPCO) est sous-diagnostiquee en raison de la mauvaise connaissance de la maladie et de la banalisation des symptomes. Methodes L’enquete IBIS (Information sur la BPCO pour un Impact Sanitaire) a ete menee aupres d’un echantillon representatif de la population francaise de plus de 40 ans (N = 2 758), pour evaluer les symptomes respiratoires et le niveau de connaissance de la maladie chez les sujets a risque ou presentant une BPCO (N = 860 soit 31 % de l’echantillon initial). Resultats Dans cet echantillon, 40 % des sujets presentaient une dyspnee de grade MRC ≥ 1 mais seuls 9 % rapportaient spontanement une gene respiratoire. Chez ces derniers, 72 % rapportaient une limitation de leurs activites quotidiennes mais seulement 14 % consideraient etre severement atteints. Une tres faible proportion de sujets (N = 220, 8 %) connaissait le terme BPCO et seuls 66 % dʼentre eux associaient la BPCO a une maladie respiratoire. Conclusions Il existe donc un ecart important entre la forte proportion de sujets a risque dans la population, la frequence de l’essoufflement chez ces sujets, la mauvaise connaissance de la maladie et la faible perception des symptomes. Ces resultats incitent a intervenir pour augmenter la connaissance de la BPCO dans la population.

Data on the individual and collective impact of chronic airflow obstruction at a population level are scarce. In a nationwide survey, dyspnoea, quality of life and missed working days were compared between subjects with and without spirometrically diagnosed chronic airflow obstruction. Subjects aged > or =45 yrs were recruited in French health prevention centres (n = 5,008). Results of pre-bronchodilator spirometry and questionnaires (European Community Respiratory Health Survey-derived questionnaire and European quality of life five-dimension questionnaire) were collected. Adequate datasets were available for 4,764 subjects aged 60+/-10 yrs (only 2% were aged > or =80 yrs). The prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity of

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. Objective and Methods: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 µg once daily or placebo for 12 weeks. Results: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 ± 0.08 liters) and 84 (0.20 ± 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 ± 0.07 liters) and 84 (0.15 ± 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 ± 12 (day 42) and 36 ± 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George’s Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. Conclusion: Tiotropium 18 µg once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

Guidelines for the management of adult lower respiratory tract infections (LRTIs) were first published by a Task Force of the European Respiratory Society (ERS) in 1998 [1]. In 2005, a completely revised version was produced, this time by a joint Task Force of the ERS and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) [2]. They used up-to-date methodology for guideline development, including a transparent and objective systematic literature search strategy, and evidence and recommendation grading [2]. Now, 6 yrs later, a joint Task Force of the two Societies, using the same methodology as in 2005, has produced a further update of these guidelines incorporating publications through to May 2010. The Task Force included an epidemiologist with expertise in guideline methodology and experts in the specialty areas relevant to LRTI management, including general practice, microbiology, infectious diseases, respiratory medicine, intensive care and public health. A short version of the guidelines containing only the recommendations has now been published in Clinical Microbiology and Infection [3], with more detailed versions available on each Society’s website. The guidelines cover the breadth of adult community-acquired respiratory infection, including prevention (both vaccine- and nonvaccine-related), infections in the community and infections in those admitted to hospital, including pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD) and exacerbations of bronchiectasis. The …

Resume Introduction La broncho-pneumopathie chronique obstructive (BPCO) represente un probleme de sante publique a l’impact economique mal evalue. Materiel et methodes SCOPE est une etude observationnelle economique, prospective et retrospective, menee en France en 2001, aupres de 114 medecins generalistes et 57 pneumologues. Son objectif est de decrire la prise en charge des patients atteints de BPCO et d’en evaluer le cout annuel en fonction du stade de severite. Des questionnaires ont permis de recueillir des informations sur les consommations de soins pendant douze mois, pour deux cent quatre-vingt cinq patients. Resultats L’analyse economique etait de type cout de la maladie en « prevalence ». La severite des troubles et la consommation de soins etaient plus importantes chez les patients suivis par un pneumologue. La BPCO et ses complications (suivi habituel du patient, exacerbations, autres complications) sont responsables de 66 % des couts, les 34 % restants n’etant pas lies a la maladie respiratoire et a ses complications. Les principaux postes de depenses etaient les hospitalisations (35 %, soit 1 509,9 euros/an/patient) et les medicaments (31 %, soit 1 340,6 euros/an/patient). Le cout direct total augmentait avec le stade de severite de la maladie, essentiellement du fait des depenses d’hospitalisation et d’assistance respiratoire. Discussion Cette etude confirme l’impact economique de la prise en charge de la BPCO en France. Des mesures permettant de ralentir l’evolution des troubles et de prevenir les exacerbations pourraient en reduire les couts.

Resume Etat des connaissances Les complications respiratoires apres chirurgie d’exerese pulmonaire sont les plus frequentes, constituant une cause non negligeable de mortalite. L’utilisation de la VNI dans les decompensations respiratoires aigues est maintenant bien reconnue. L’utilisation « preventive » de la VNI en l’absence d’IRA et/ou d’hypercapnie peut egalement se justifier par les benefices physiologiques attendus en periode post operatoire de chirurgie pulmonaire. L’objectif de notre etude est donc d’evaluer l’efficacite de la VNI en postoperatoire immediat dans les BPCO moderees a severes pour la prevention des complications pulmonaires. Methodes Il s’agit d’une etude prospective multicentrique randomisee selon un schema parallele en ouvert menee sur des patients porteurs d’une BPCO moderee a severe hospitalises en chirurgie thoracique pour resection pulmonaire. Resultats attendus Il s’agit de determiner si la mise en route d’une VNI en post-operatoire immediat permet de diminuer l’incidence des evenements aigus respiratoires (insuffisance respiratoire aigue) et d’analyser si des sous groupes beneficient plus de la VNI. Cette etude devrait permettre de situer l’interet de la VNI en post-operatoire immediat d’une chirurgie pulmonaire de resection pulmonaire.

Background: Chlorofluorocarbons (CFCs) have traditionally been used as propellants in pressurized metered- dose inhalers (pMDIs), which are often used to deliver drugs to the lungs for the treatment of reversible obstructive airways diseases. However, CFCs are harmful to the environment and need to be phased out. Hydrofluoroalkanes (HFAs), such as HFA-134a, represent a safe alternative to CFC propellants for use with pMDIs. Formoterol fumarate has been recently formulated in an HFA-134a-containing pMDI and is undergoing clinical testing with the aim of providing an effective, safe and environmentally-friendly alternative to currently existing formulations. Objectives: The study objective was to demonstrate the non-inferiority (clinical equivalence) of the HFA-134a-propelled formoterol pMDI versus the formoterol Aerolizer™ dry powder inhaler (DPI). Methods: The study was a single dose, double-blind, double-dummy, randomized, placebo and reference product controlled, three-periods, crossover trial in 49 patients with moderate-to-severe stable asthma. The active treatments involved a single 12-µg dose of formoterol delivered from an HFA-134a-propelled pMDI and an Aerolizer™ DPI. The primary efficacy parameter was the average 12-hour forced expiratory volume in 1 s (FEV1), calculated as area under the 12-hour post-morning dose FEV1 time curve divided by time (hours). Results: Mean 12-hour average FEV1 was 2.28 liters for placebo, 2.60 liters for formoterol pMDI and 2.60 liters for the formoterol DPI. Contrast analysis showed that the HFA-propelled formoterol pMDI was significantly superior to placebo in terms of 12-hour average FEV1. Further statistical analysis confirmed bronchodilation with the pMDI formoterol formulation which was clinically equivalent to that seen with the DPI formoterol formulation. All treatments were well tolerated. Conclusions: The bronchodilatory effect of a 12-µg dose of formoterol inhaled from a CFC-free, HFA-propelled pMDI is significantly superior to placebo and equivalent to a commercially available formoterol DPI.

Resume Introduction La notion d’index therapeutique (rapport efficacite-tolerance ou benefice-risque) est un determinant majeur des decisions therapeutiques dans l’asthme. Methodes Au numerateur, l’index therapeutique depend de l’efficacite (effet maximal) et non de la puissance (rapports de dose entre produits, issus des relations dose-effet). Au denominateur, de multiples facteurs pharmacologiques influencent la tolerance. L’acceptabilite des effets secondaires compte-tenu des objectifs therapeutiques doit aussi etre prise en compte. Resultats Dans l’asthme, certaines strategies ont fait preuve d’un index therapeutique plus favorable que d’autres : par exemple, l’association d’un traitement additionnel (beta2 agonistes inhales de longue duree d’action, anti-leucotriene, theophylline) a une corticotherapie inhalee s’avere d’un meilleur index therapeutique que le doublement des doses de celle-ci lorsque la maladie n’est pas controlee. En revanche, la comparaison des index therapeutiques de differentes molecules de corticosteroides inhales est beaucoup plus difficile. Conclusions La possibilite d’effets secondaires systemiques lors de l’utilisation a long terme de fortes doses de corticosteroides inhales doit conduire a en rechercher la dose minimale efficace.

Objective The main objective of the SCOPE study was to estimate the total direct medical costs of patients with treated chronic obstructive pulmonary disease (COPD) in France according to severity stages. Methods Total medical resources consumption of a sample of COPD patients was collected over a 12-month period through a national physician survey (including both general practitioners and lung specialists). This survey was completed for 255 patients. Data were then extrapolated to all patients with diagnosed and treated COPD in France. Average total medical resources consumption of a COPD patient per year was €4366. Among this cost 41% was directly related to COPD follow-up, 25% to COPD-related complications (mainly exacerbations), and 34% to other diseases. More than one-third of the total direct COPD cost was related to hospitalizations and 31% to drug consumption. COPD-related costs increased markedly with severity based on FEV 1 (but data suggested the existence of a threshold effect). SCOPE data did not show any evidence of a significant relationship between direct medical cost and patient age, sex, addiction to tobacco, or duration of COPD. The total medical consumption of COPD patients in France was €3.5 billion and accounted for 3.5% of the total medical expenditures (prevalence of COPD was estimated 1.3% in the general population). Results The SCOPE study revealed the high level of medical resources consumption of patients with COPD. Conclusions The burden of COPD itself and its complications appeared to be of considerable magnitude in France especially for severe COPD.

Acute respiratory failure and infectious pneumonia are the major causes of death during induction chemotherapy of acute leukemia. However, the causes, incidence and prognostic value of all respiratory events (REs) occurring in this context have never been assessed prospectively. We recruited 65 consecutive patients with newly diagnosed acute leukemia into a 1-year prospective study (December 2000-November 2001) to evaluate the incidence and prognostic value of these events. REs were frequent: 38 were recorded in 30 patients. There was a significant relationship between REs and pre-existing respiratory disease and/or smoking. REs were caused by infection in 34% of cases, by an established cause other than infection in 42% and had an undetermined cause in 24%. Poor early outcome (death within 45 days of starting induction chemotherapy) in patients experiencing an RE was independently associated with a25/min respiratory rate (P=0.003) and the nonachievement of complete remission (CR) (P0.0001). Predictors of overall survival in the entire patient population were the absence of CR (P0.0001), REs (P=0.02) and aor =2 performance status (P=0.03). In conclusion, REs are frequent during induction chemotherapy of acute leukemia and represent an independent prognostic factor of poor outcome, regardless of their cause.

Prognosis of patients with non small cell lung cancer (NSCLC) remains difficult to assess, even after adjustment for pathological stage. Prognostic value of numerous biological markers has been evaluated, with conflicting results. Data of 86 patients with NSCLC treated by surgery were collected with clinical characteristics, histopathological data including tumor differentiation and status of blood and lymphatic vessel invasion and evaluation by immunohistochemistry of Rb, Bcl-2 and Ki-67 expression. Prognostic values for overall survival (OS) and event-free survival (EFS) were analyzed by the log tank test and the multivariable Cox model. Using univariable analyses, pT, pN, poor differentiation or large cell subtype were associated with a poor OS, while lymphatic and/or blood vessel invasion were associated with a short EFS. None of the molecular markers had a significant prognostic value for either outcome. In multivariable analyses, only stage remained of prognostic value for OS. Interestingly, the presence of blood vascular invasion in the tumor was significantly predictive for subsequent metastatic occurrence in stages I and II. This feature might, therefore, be relevant for administration of adjuvant therapy in completely resected NSCLC.

The role of the new class of fluoroquinolones in the treatment of acute bacterial exacerbations of chronic bronchitis involves the complex context of drug prescription in such situations. This is based on the probability of an infectious bacterial etiology, whether concerning a bronchial infection or pneumonia; and on the severity of the underlying respiratory disease and associated functional impairment. The most frequently encountered pathogenic agents infecting the respiratory tract are Streptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis, which have a common characteristic: a growing resistance to the usual antibiotics, in particular the aminopenicillins. The investigation carried out on anti-pneumococcal third-generation fluoroquinolones and their use in the treatment of bacterial exacerbations of chronic bronchitis has consisted of equivalence studies, aimed at demonstrating the superiority of one antibiotic compared to another. These investigations are characterized by a wide heterogeneity in populations, associated treatment and follow-up, and by a widespread uncertainty regarding the infectious nature of the exacerbation. The therapeutic success rate varies between 70 and 90%, with a frequently favorable tendency in terms of clinical and bacteriological efficacy recorded for the new fluoroquinolones. Chronic bronchitis is one of the most frequently encountered respiratory disorders. Its increasing prevalence renders it a major public health problem. The excessive prescription of antibiotics in cases of chronic bronchitis can have serious economic and environmental consequences. However, insufficient treatment of an acute bacterial exacerbation only aggravates the deterioration of respiratory function and negatively affects patient prognosis. In this pathological context, the possible role of fluoroquinolones that are active against pneumococci has been discussed in the light of recent clinical findings reported in the literature.

The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12–8039) with that of co-amoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the co-amoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB.

The inhalation route is widely used for the treatment of obstructive lung diseases, because administered drugs have a high therapeutic index as they reach their target directly; this requires that they be of adequate size to penetrate the conducting airways, i.e. 2-5 microns. Pressurized inhalers were the first reliable metered-dose devices available, and are still the most frequently used. However, metered-dose inhaler (MDI) suspensions will have to be reformulated: they contain chlorofluorocarbons (CFCs), whose production has to be stopped within a few years, as they affect the stratosphere. Another limitation of MDI usage is paradoxical bronchospasm; this phenomenon, however, occurs in a low number of patients and is rarely clinically relevant. The main cause of concern with MDIs is their misuse by more than 50% of patients, which leads to a reduced lung deposition and clinical efficacy. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers (DPIs), and breath-actuated MDIs have been shown to increase lung deposition of drugs in poor coordinators. However, all have limitations which may have varying consequences on clinical efficacy: cumbersome dimensions of spacers, effect of inspiratory flow rate and humidity on lung deposition of dry powders, need for reformulation with CFC-free gases for breath-actuated pressurized inhalers. Reformulation of MDI aerosols is a complex procedure, which may not be feasible for all drugs. The new products need extensive toxicological and clinical testing, as some of their characteristics may differ from those of their predecessors.

A questionnaire survey was performed on the use of investigations and their impact on treatment of adult lower respiratory tract infection in the community. Data on the management of 2,056 such infections were obtained simultaneously from general practitioners in France, Germany, Italy, Spain and the UK. Diagnostic tests were only performed in 29% of cases. Chest radiographs were performed most frequently (22%), followed by peripheral blood white cell count (15%) and microbiological examination of sputum (7%), with major differences being found in the frequency of these tests both by clinical diagnosis and country. A change in initial antibiotic therapy was made in 12% of cases, with use of investigation being significantly linked to such changes. Second- and third-line antibiotics were significantly different to first-line therapy, with macrolides the most frequently prescribed second-line and quinolones the most frequently prescribed third-line antibiotics.

RESUMO: O objectivo do estudo, multicêntrico e multinacional, foi o de comparar a efectividade do tratamento oral de 5 dias de moxifloxacina com o tratamento antibiótico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina) nas EABC.Mil novecentos e trinta e cinco doentes foram seleccionados segundo os seguintes critérios: idade superior a 45 anos com bronquite crónica estável, carga tabágica superior a 20 UMA, 2 ou mais EACB no último ano e FEV1 inferior a 85% da referência (estado basal pré-exacerbação).A randomização de 733 doentes, estratificada por corticoterapia associada ou não, foi efectuada na presença de uma EABC que cumprisse os critérios de Anthonisen de tipo I em dois braços: 5 dias de moxifloxacina (400 mg/d) versus 7 dias de um de 3 antibióticos seleccionados pelo investigador, segundo os seus próprios critérios clínicos; amoxicilina (500 mg 3xd), cefuroxime (250 mg 2xd) ou claritromicina (500 mg 2xd).A avaliação primária de resultados consistiu no sucesso clínico (melhoria clínica e não haver necessidade de mudança de antibiótico) e as secundárias, cura clínica (regresso ao estado basal pré-exacerbação), necessidade subsequente de antibioterapia, tempo até à próxima exacerbação e sucesso bacteriológico.As avaliações subsequentes à randomização foram efectuadas 7 a 10 dias após o início do tratamento e mensalmente até a uma nova exacerbação ou decorridos 9 meses.A moxifloxacina foi equivalente aos outros antibióticos na variável primária â sucesso clínico (87,6% vs 83%).No entanto, a moxifloxacina foi significativamente superior na cura clínica (70,9% vs 62,8%) e sucesso bacteriológico (91,5% vs 81%). Cerca do dobro dos doentes no braço antibiótico convencional (14,1%) necessitaram de antibioterapia sistémica subsequente contra 7,6% no braço moxifloxacina.A superioridade da moxifloxacina em relação à terapêutica de referência manteve-se quando se consideraram os subgrupos de prognóstico, nomea-damente o número de exacerbações no ano anterior, idade dos doentes, obstrução das vias aéreas, duração da doença e doenças concomitantes (nomeadamente cardíaca)A moxifloxacina demonstrou uma erradicação bacteriológica superior na população microbiologicamente válida (devido, em grande parte, à persistência de H. influenzae nos grupos de referência).Foi utilizado um número significativamente maior de antibióticos para tratamento das exacerbações no grupo dos fármacos de referência durante o período de seguimento, devido a falências terapêuticas neste grupo, comparativamente com a moxifloxacina.O tempo até à próxima exacerbação foi significativamente superior com moxifloxacina (131 dias vs 103 dias) e a ocorrência de falência, nova exacerbação ou novo antibiótico foi muito inferior até aos 5 meses. COMENTÃRIOS: Está demonstrada a eficácia da terapêutica antibiótica no tratamento das EABC do tipo I e do tipo II de Anthonisen.à com base nestes critérios que os estudos com antibióticos têm sido realizados comparando a ânão inferioridadeâ (equivalência) clínica e bacteriológica dos mais recentes antibióticos â β-lactâmicos (com inibidores das blactamases), cefalosporinas, macrólidos e quinolonas â relativamente aos mais antigos (ampicilina, tetraciclina e cotrimoxazole).No entanto, estes estudos têm excluído doentes graves, com comorbilidades, assim como não estudam apenas doentes com DPOC (isto é, com obstrução das vias aéreas), pois incluem doentes de idades mais jovens e ainda sem obstrução.Este estudo MOSAIC foi desenhado para avaliar a eficácia do tratamento das exacerbações infecciosas (critérios de Anthonisen) em doentes com DPOC (obstrução) de 5 dias com moxifloxacina comparativamente a um regime terapêutico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina).Este é o primeiro estudo concebido especificamente para avaliar a efectividade de um antibiótico (moxifloxacina) nas exacerbações infecciosas de doentes com DPOC.à de lamentar que estes doentes sejam aqui designados de bronquíticos crónicos, o que não é rigoroso, mas parece que os motivos se prendem com a aprovação pelas entidades reguladoras dos medicamentos.Outro aspecto também ligado à aprovação por essas entidades prende-se com a demonstração de equivalência clínica de um novo antibiótico, o que ficou demonstrado neste estudo.Ora, se é equivalente, porquê utilizar o antibiótico mais recente, se os antibióticos mais convencionais atingem taxas de sucesso iguais quando avaliadas aos 7 a 10 dias?Este é o aspecto fundamental deste estudo, e a utilizar em futuros ensaios, uma vez que fica demonstrado que parâmetros de médio e longo prazos (superiores aos 7 a 10 dias) na DPOC são fundamentais como critérios de avaliação de efectividade clínica de um novo antibiótico nas exacerbações agudas da DPOC.Aguardam-se os resultados deste estudo no que respeita à qualidade de vida e à fármaco-economia.Por fim, é de salientar que este estudo contou com a participação de 2 centros portugueses (H. Pulido Valente Dr.ª Cecília Nunes, e H. S. João Dr. João Almeida), o que nem sempre acontece com outros estudos multinacionais no âmbito da DPOC e asma.

Resume Les symptomes de la tuberculose ne sont pas le plus souvent d'emblee evocateurs : ce qui doit suggerer la tuberculose est l'existence de facteurs de risque pour cette maladie et la chronicite des symptomes. Les malades consultent leur medecin avec des delais tres variables qui dependent de facteurs qui ne sont pas encore tres bien identifies ; les medecins evoquent plus volontiers ce diagnostic s'ils sont familiarises avec cette maladie, ce qui sera de moins en moins frequent dans les zones de basse prevalence pour la tuberculose. L'etape-cle est la radiographie thoracique qui est tres souvent tres suggestive et mene par le recours a la bacteriologie ou par l'existence d'elements diagnostiques convergents a la mise en oeuvre du traitement.

To investigate Freund's adjuvant-induced changes in respiratory epithelial permeability, we determined the respiratory epithelium clearance of 99mTc-DTPA (RC-DTPA) in rats and the localization of horseradish peroxidase (HRP) across the lung epithelium. RC-DTPA was determined before and after intravenous injection of saline (control) or complete Freund's adjuvant (CFA). Although the respiratory epithelium was not disrupted, RC-DTPA was increased 15 min after injection of CFA and was still high after 3 d but had returned to normal after 7 d, after which it again increased and stayed high from Day 42 through Day 112. Cell number obtained by bronchoalveolar lavage increased from 15 min to 3 d after injection of CFA. Lung granulomatosis was observed 14 to 112 d after injection of CFA; changes in RC-DTPA correlated with changes in alveolar cells. HRP was present in bronchiolar intercellular spaces only in the CFA group. We conclude that (1) RC-DTPA increases in rat lung CFA granulomatosis 15 min to 3 and 42 to 112 d following injection, (2) the increase in RC-DTPA is not related to a rupture of epithelium but (3) is proportional to the cell influx into the lung, and (4) is possibly caused by the opening of tight junctions in small airways.

Rationale: Both obesity and obstructive sleep apnea (OSA) are risk factors for hypertension (HT) and chronic heart failure (CHF). The association between OSA and COPD (overlap syndrome) and the obesity hypoventilation syndrome (OHS) have been proposed as leading to enhanced cardiovascular risk. Methods: 3093 obese subjects (IMC>30kg/m2) referred for suspicion of OSA were prospectively assessed by sleep studies, lung function tests and blood gazes. For the whole group, mean age was 57±13 years with 66% of men, mean BMI: 36.8±6.2 kg/m2, 52.8% of the subjects being hypertensive and 3.23% suffering from CHF. 926 of the 3093 did not exhibit OSA or COPD. Results: In multivariate analysis, prevalent hypertension was associated with OSA (Odd ratio (OR): 1.23 (confidence intervals (CI): 1.04-1.45), p=0.015), ≥2 nocturia episodes per night (OR: 1.295 (CI: 1.10-1.52), p

Exacerbations of COPD are common and cause a considerable burden to the patient and the healthcare system. To optimize the hospital care of patients with exacerbations of COPD, clinicians should be aware of some key points: management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define those patients requiring hospital admission and those who could be managed as outpatients. In hospitalized patients, the appropriate level of care should be determined by the initial severity and response to initial medical treatment. Medical treatment should follow recent recommendations, including rest, titrated oxygen therapy, inhaled or nebulized short-acting bronchodilators (Beta2-agonists and anticholinergic agents), DVT prevention with LMWH, steroids in most severely ill patients, unless there are contraindications and antibiotics in the case of a clear bacterial infectious aetiology. Severe exacerbations may lead to acute hypercapnic respiratory failure. Unless contraindicated, non-invasive ventilation (NIV) should be the first line ventilatory support for these patients. NIV should be commenced early, before severe acidosis ensues, to avoid the need for endotracheal intubation and to reduce mortality and treatment failures. Several randomised controlled clinical trials support the use of NIV in the management of acute exacerbations of COPD, demonstrating a decreased need for mechanical ventilation and an improved survival. In most severe cases, NIV should be provided in ICU. Although it has been shown that for less severe patients (with pH values7.30), NIV can be administered safely and effectively on general medical wards, a lead respiratory consultant and trained nurses are mandatory. Mechanical ventilation through an endotracheal tube should be considered when patients have contraindications to the use of NIV or fail to improve on NIV. The duration of mechanical ventilation should be shortened as much as possible by an early weaning process, including preventive post-extubation NIV in hypercapnic patients. hospital stay could be shortened by non-invasive treatments. Future exacerbations should be avoided by respiratory specialist management of the patients, including education, optimization of long-term medical treatment, vaccinations, nutritional support, and pulmonary rehabilitation.

A 60 year old male patient was admitted to hospital with pulmonary and cerebral abscesses. A percutaneous lung biopsy under CT scanning showed actinomycosis. After 4 weeks antibiotic therapy with ceftriaxone and metronidazole there was an improvement in the pulmonary lesion but new cerebral lesions appeared. A neurosurgical cerebral biopsy showed evidence of metastatic squamous carcinoma, probably of pulmonary origin. The diagnosis had been delayed by the presence of the actinomycosis. His general condition did not permit anti-tumour treatment and the patient soon afterwards. In the presence of pulmonary actinomycosis an associated malignancy should be excluded.

We report the case of a 61-year old man in whom a deep venous thrombosis was the presenting feature of disseminated lung carcinoma. A few days later, an arterial thrombosis occurred necessitating amputation. Within a few weeks, the lung cancer progressed dramatically and the patient died. While the association between venous thrombosis and cancer is well known, the relationship between cancer and arterial thrombosis has been less explored. This observation allows discussion of the pathophysiological and clinical aspects of this association, as well as the implications for patient care.

Chronic obstructive pulmonary disease (COPD) is markedly under-diagnosed, which may relate to under-reporting of symptoms and poor awareness of the disease.A survey was conducted in a sample of the French general population aged 40-75 years (n=2758) to assess respiratory symptoms and level of knowledge of the disease in subjects with or at-risk of COPD (n=860, 31%).The high frequency of dyspnoea (MRC dyspnoea gradeor =1: 40%) contrasted with that of subjects spontaneously reporting respiratory problems (9%). Among these, 72% reported limitations in daily-life activities but only 14% considered that they were severely affected by their respiratory status. A very low proportion of subjects knew the term COPD (8%) and only 66% of these associated COPD with a respiratory disease.There is a wide gap between the high number of subjects at risk of COPD in the general population and the frequency of breathlessness in these subjects on one hand, and the poor knowledge of the disease, poor perception of symptoms, and under-diagnosis and under-use of spirometry on the other. Increasing awareness of COPD in the population is needed.

Tobacco smoking is the leading cause of COPD worldwide but other risk factors have been recognized. Air pollution is one of them, but its exact role in the development of COPD is hard to demonstrate. Its physiological effects on lung function have only been studied since the nineties by long and tedious cohort studies. Difficulties arise from the heterogeneity of air pollution (gas and particles); thus, its respiratory effects have to be examined for every component separately, and in different populations. It is also necessary to analyse the effects of atmospheric pollution in the short and the long term, considering both its physiological, clinical and toxicological effects, from childhood to adulthood. These factors make it difficult to obtain statistically significant results. Nevertheless, most studies seem to point to a role of air pollution in the development of COPD via oxydative stress but further studies are needed to confirm the exact effect of each component of air pollution on the respiratory tract. These studies could lead to improved public health policies and results are awaited that would identify at-risk populations, decide appropriate preventive measures and propose documented thresholds in pollution exposure... thereby limiting the spread of COPD.

Summary Introduction Chronic obstructive pulmonary disease (COPD) is underdiagnosed because of limited disease awareness with trivialization of the symptoms in the general population. Methods A survey was conducted in a representative sample ( n = 2758) of individuals older than 40 years of age in the general population of France. Respiratory symptoms and knowledge about COPD were assessed in individuals with or at risk for COPD ( n = 860, 31% of the sample). Results In the overall sample, 40% of individuals had a Medical Research Council dyspnea grade of 1 or more but only 9% spontaneously reported shortness of breath. Of these 9%, 72% reported limitations to their daily activities but only 14% believed they had severe lung disease. In the overall sample, only 220 (8%) individuals knew the term COPD and only 66% associated the term COPD with respiratory disease. Conclusions Despite a large proportion of individuals at risk for COPD or having COPD and a high prevalence of breathlessness, awareness of respiratory symptoms and knowledge of COPD were limited. These findings indicate a need for educating the general population about COPD.

Summary Background Lung deposition is crucial for asthma treatment. However, there is no study comparing the potential role of lung co-deposition of combination therapy (inhaled corticosteroid and long-acting β2 agonist) in the same inhaler. In moderate to severe asthmatics, an extra-fine hydrofluoroalkane combination of beclomethasone dipropionate and formoterol given via a single pressurised metered-dose inhaler (pMDI) was compared with beclomethasone dipropionate chlorofluorocarbon (CFC) pMDI and formoterol dry powder inhaler (DPI) given via separate inhalers. Methods In a double-blind, double-dummy, 24-week randomised clinical trial, 645 patients with moderate to severe asthma uncontrolled by regular treatment with inhaled corticosteroids received regular treatment with extra-fine fixed combination beclomethasone dipropionate 200μg/formoterol 12μg bid, or beclomethasone dipropionate (500μg bid) via CFC pMDI and formoterol (12μg bid) via DPI, or beclomethasone dipropionate (500μg bid) via CFC pMDI. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included lung function measured at clinic, asthma symptoms and control, exacerbations. Results Beclomethasone dipropionate/formoterol combination via single inhaler or via separate inhalers improved morning PEF. However, the combination via single inhaler was more effective than given via separate inhalers for asthma control. Both combination treatments were superior to beclomethasone dipropionate alone in improving lung function and asthma control. All treatments were well tolerated. Interpretation In patients with moderate to severe asthma, beclomethasone dipropionate/formoterol in a single inhaler was as effective as beclomethasone dipropionate plus formoterol and superior to beclomethasone dipropionate alone in improving lung function. For the first time with a single inhaler, beclomethasone dipropionate/formoterol was significantly superior to separate components for asthma control. This trial is registered with ClinicalTrials.gov , number NCT00476268 .

In patients with hematological malignancy (HM) developing acute respiratory failure (ARF) bronchoalveolar lavage (BAL) is considered as a major diagnostic tool. However, the benefit/risk ratio of this invasive procedure is probably lower in the subset of patients with acute myeloid leukemia (AML). The study was to analyze the yield of BAL performed in HM patients (n=175) with AML or lymphoid malignancies (LM) admitted in intensive care unit (ICU) for ARF and pulmonary infiltrates. BAL was performed in 121 patients (53/73 AML patients (73%) and 68/102 LM patients (67%)) without a definite diagnosis at admission or contraindication for fiberoptic bronchoscopy. Life-threatening complications were noticed in 12/121 patients (10%). The overall diagnostic yield of BAL was 47% (25/53) in AML patients and 50% (34/68) in LM patients. A microorganism was recovered from BAL in 23% (12/53) of AML patients and 41% (28/68) of LM patients (P

The follow-up of Community Acquired Pneumonias (CAP) and Acute Exacerbations of Chronic Obstructive Pulmonary Diseases (AECOPD) differs with the setting of care, but overall calls upon the same investigations as the initial evaluations. In the event of initial ambulatory care, the evaluation is carried out primarily on clinical data, at the 2 or 3rd day for the CAP, at the 2nd to 5th day for the AECOPD. In the event of unfavourable evolution, or from the start in the most severe cases, the follow-up is carried out in hospital; clinical evaluation is readily daily, and all the more frequent that the clinical condition is worrying because of the severity or risk factors. The investigations will be limited to those initially abnormal in the event of favourable evolution; on the contrary, unfavourable evolution can justify new investigations which depend on clinical characteristics. Remotely, i.e. 4 to 8 weeks later, must be checked the return at the baseline clinical state, a chest X-ray (CAP), spirometry and arterial blood gas (AECOPD), even bronchoscopy and thoracic CT-scan.

Chronic obstructive pulmonary disease (COPD) is amajor cause of handicap, mortality and health careexpenses (1). Altered quality of life (QOL) is a hallmarkof the disease, and relates mainly to dyspnoea andexacerbations: both QOL at steady-state and its rate ofdecline over time correlate to the frequency of acuterespiratory events (2, 3). In parallel, hospitalizations forexacerbations in the most severe patients are importantdeterminants of health care costs (4). Thus, preventingexacerbations is a major goal of care for COPD patients,both from an individual and collective point of view.Inflammation and COPD exacerbationsIn most cases, COPD occurs in smokers and ex-smokers,in whom airflow limitation is the consequence of variousdegrees of emphysema, chronic bronchiolitis and mucusplugging (5). These components of the disease have beenlinked to inflammatory and remodelling processes in theairways and lung parenchyma, involved inflammatorycells being mainly neutrophils, B and T lymphocytes andmacrophages (5, 6). Airways inflammation is moreintense during exacerbations, as shown by increases inthe levels of (i) expression of neutrophil elastase, CXCL-5, CXCL-8 and CXCR1/2 in biopsies (7), (ii) exhaledLTB4 and 8-isoprostane in breath condensates (8), (iii)interleukin (IL)-8 and tumour necrosis factor (TNF)-a insputum (9).Infections are a leading cause of exacerbations andfurther amplify airway inflammation (10). However,about one half of exacerbations occur in the absence ofany detectable infective pathogen, which may not preventinflammation from increasing (11). Besides, higher levelsof inflammatory markers in the airways of patients atsteady-state are also associated with more frequentexacerbations (12). Studies of the East London COPDcohort even suggest the existence of a particular subgroupof COPD patients called frequent exacerbators, whoconsistently have more than 2–3 exacerbations per year(13). In these patients, QOL is more altered, forcedexpiratory volume at 1 s (FEV

Background: Whether sputum microbiological examination should be performed systematically in hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. Objectives: To assess the yield of sputum microbiological examination in COPD patients hospitalized in a medical ward for an acute exacerbation with purulent sputum. Methods: Two hundred consecutive exacerbations in 118 patients were studied. Patients underwent sputum microbiological examination on admission and baseline lung function tests and CT scans were recorded. Factors associated with positive culture were analyzed. Results: Sputum culture was positive (≧107 CFU/ml) in 59% of samples, Haemophilus influenzae and Streptococcus pneumoniae being the most frequent pathogens. Factors associated with positive culture were bronchiectasis, long-term oxygen therapy and low FEV1. Pseudomonas spp. were found in 8.5% of all patients, who all had a FEV1 25 leukocytes but >10 epithelial cells per field. Microbiological results induced a change in antibiotic therapy in 43.9% of cases with both quality criteria but also in 25.2% of cases with only one quality criterion. Finally, a predominant aspect after Gram stain was found in all positive samples. Conclusions: These data suggest that sputum microbiological examination with direct examination and leukocyte count should be performed routinely in patients hospitalized for COPD exacerbations with purulent sputum, especially when FEV1 is less than 50% predicted and in patients with bronchiectasis.

Chronic obstructive pulmonary disease (COPD) is a major health problem. Few data about COPD economic burden are available.SCOPE was an observational economical retrospective and prospective study conducted in France in 2001, by 114 general practitioners (GPs) and 57 lung specialists. The aim was to describe the burden of COPD patients and to estimate the annual cost according to severity stages. Health resource utilization was collected by questionnaires over a 12-month period for 285 patients.It was a cost-of-illness analysis. COPD patients followed by a lung specialist were more severe than patients followed by a GP and had a higher level of medical resource consumption. The COPD disease and its complications explained 66% of the total cost. The main cost drivers were inpatient care (35%, or 1509,9 euros/year/patient) and prescription medications (31%, or 1340,6 euros/year/patient). The direct total cost varied according to COPD severity on account of inpatient care and respiratory assistance.This study confirmed the economic burden of COPD in France. Actions allowed to slow down the disease's evolution and to anticipate the exacerbation could reduce the cost.

Respiratory complications are common following pulmonary resection and cause a significant mortality. The use of non-invasive ventilation (NIV) in acute respiratory insufficiency (ARI) is now well recognised. The prophylactic use of NIV in the absence of ARI and/or hypercapnia may be equally justified for the physiological benefits expected in the post-operative period following pulmonary surgery. The aim of our study therefore is to evaluate the effectiveness of NIV in the prevention of pulmonary complications in the immediate post-operative care of patients with moderate and severe COPD.It will be a multicentre, prospective, randomised, parallel, open ended study of patients with moderate and severe COPD admitted to hospital for pulmonary resection.To determine whether the setting up of NIV immediately post-operatively reduces the incidence of acute respiratory events (acute respiratory insufficiency) and to identify any sub-groups who receive greater benefit from NIV. This study should establish the place of NIV in the immediate post operative care following pulmonary resection.

Chlorofluorocarbons (CFCs) have traditionally been used as propellants in pressurized metered-dose inhalers (pMDIs), which are often used to deliver drugs to the lungs for the treatment of reversible obstructive airways diseases. However, CFCs are harmful to the environment and need to be phased out. Hydrofluoroalkanes (HFAs), such as HFA-134a, represent a safe alternative to CFC propellants for use with pMDIs. Formoterol fumarate has been recently formulated in an HFA-134a-containing pMDI and is undergoing clinical testing with the aim of providing an effective, safe and environmentally-friendly alternative to currently existing formulations.The study objective was to demonstrate the non-inferiority (clinical equivalence) of the HFA-134a-propelled formoterol pMDI versus the formoterol Aerolizer dry powder inhaler (DPI).The study was a single dose, double-blind, double-dummy, randomized, placebo and reference product controlled, three-periods, crossover trial in 49 patients with moderate-to-severe stable asthma. The active treatments involved a single 12-microg dose of formoterol delivered from an HFA-134a-propelled pMDI and an Aerolizer DPI. The primary efficacy parameter was the average 12-hour forced expiratory volume in 1 s (FEV1), calculated as area under the 12-hour post-morning dose FEV1 time curve divided by time (hours).Mean 12-hour average FEV1 was 2.28 liters for placebo, 2.60 liters for formoterol pMDI and 2.60 liters for the formoterol DPI. Contrast analysis showed that the HFA-propelled formoterol pMDI was significantly superior to placebo in terms of 12-hour average FEV1. Further statistical analysis confirmed bronchodilation with the pMDI formoterol formulation which was clinically equivalent to that seen with the DPI formoterol formulation. All treatments were well tolerated.The bronchodilatory effect of a 12-microg dose of formoterol inhaled from a CFC-free, HFA-propelled pMDI is significantly superior to placebo and equivalent to a commercially available formoterol DPI.