[Physiotherapy and COVID-19. From intensive care unit to home care-An overview of international guidelines]. / Kinésithérapie et COVID-19 : de la réanimation à la réhabilitation à domicile. Synthèse des recommandations internationales.

INTRODUCTION: The new coronavirus disease 2019 (COVID-19) is responsible for a global pandemic and many deaths. This context requires an adaptation of health systems as well as the role of each healthcare professional, including physiotherapists. STATE OF THE ART: In order to optimize the management of people with COVID-19, many savant societies published guidelines about physiotherapy interventions within the crisis but none offered a global overview from the intensive care unit to home care. Therefore, the aim of this review is to offer an overview of recommended physiotherapy interventions in order to facilitate the management of these patients, whatever the stage of the disease. PERSPECTIVES: Owing to the emergent character of the COVID-19, actual guidelines will have to be adjusted according to the evolution of the pandemic and the resources of the hospital and liberal sectors, in particular for the long-term follow-up of these patients. Current and future research will aim to assess the effectiveness of physiotherapy interventions for people with COVID-19. CONCLUSION: The emergence of COVID-19 required a very rapid adaptation of the health system. The role of physiotherapists is justified at every stage of patients care in order to limit the functional consequences of the disease.

[Characteristics of the patients included in the French cohort of patients with emphysema caused by alpha-1 antitrypsin deficiency]. / Caractéristiques des patients inclus dans la cohorte française de patients emphysémateux déficitaires en alpha-1 antitrypsine.

INTRODUCTION: Alpha-1 antitrypsin deficiency is associated with the occurrence of pulmonary emphysema. The aim of this study is to describe the characteristics of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema. METHODS: We describe a prospective cohort study including adult patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema confirmed by CT scan living in France. Patients' clinical and functional characteristics, quality of life measures and management were recorded every 6 months during a five-year period. RESULTS: 201 patients were included from 56 centres between 2005 and 2008. The characteristics of 110 patients have been analysed. Mean age was 50 years (SD:11.8), 62.7% were males, 90% were tobacco smokers. The main functional results (% predicted) were: FEV1: 42.8 (19.6), CPT: 128.3 (21.7), CRF: 167.0 (46.0), 6 minute walking distance (meters): 413 (130). 51 (46.4%) patients received augmentation therapy. Augmentation therapy was administered weekly (37.5%), twice a month (35.4%) or monthly (25.5%). Study centre was the only factor associated with the likelihood to received augmentation therapy. CONCLUSIONS: The clinical and functional characteristics as well as management of these patients varied markedly. There is a need for a standardization of the management of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema.

[Cohort of patients initiated to home ventilation. Observational and prospective study]. / Cohorte de patients nouvellement traités par ventilation non invasive à domicile. Étude observationnelle, prospective et multicentrique.

Cohort of patients initiated to home ventilation. Observational and prospective study. The effectiveness of home noninvasive ventilation (NIV) for chronic respiratory failure (CRF) is well established. However, few data are available about home NIV prescription and utilization according to the different etiologies of respiratory failure. The ANTADIR Federation, in partnership with the Ventilatory Support Group of the French Speaking Pulmonary Society, has set up a national, observational and multicenter cohort study. The main goal of this study is to analyze the clinical data justifying home NIV prescription in patients with chronic respiratory insufficiency. The secondary objectives will be to assess: the evolution of comorbidities or their occurrence, hospitalizations, NIV compliance, dropout and survival. The population includes patients with chronic respiratory failure newly initiated onto NIV, both in a stable state and following an acute exacerbation who qualify for long-term NIV. Data collected include: diagnosis and comorbidities, age, sex, BMI, biomarkers (hematocrit, arterial blood gases, total CO2) and functional data (FEV1, VC, TLC), nocturnal results (SaO2, PtcCO2), type of ventilator used, ventilator parameters and mask type. Follow-up data will be collected at 4 months, 1 year and 2 years and will include: hospitalizations, changes in prescription, adherence, dropouts and deaths. This work will make it possible to obtain new scientific information on long-term NIV use in France.

[Cardiopulmonary interactions in the course of mechanical ventilation]. / Interactions cœur­poumons au cours de la ventilation mécanique.

INTRODUCTION: The haemodynamic consequences of ventilation are multiple and complex and may affect all the determinants of cardiac performance such as heart rate, preload, contractility and afterload. These consequences affect both right and left ventricle and are also related to the biventricular interdependence. STATE-OF-THE-ART: Ventilation modifies the lung volume and also the intrathoracic pressure. Variations in lung volume have consequences on the pulmonary vascular resistance, hypoxic pulmonary vasoconstriction and ventricular interdependence. Variations in intrathoracic pressure have a major impact and affect systemic venous return, right ventricular preload, left ventricular preload, right ventricular afterload, left ventricular afterload and myocardial contracility. The haemodynamic consequences of positive pressure ventilation depend on the underlying chronic cardiopulmonary pathologies leading to the acute respiratory failure that was the indication for ventilation. CONCLUSION: In this review, we will focus on severe COPD exacerbation, acute left heart failure and weaning from ventilation.

[Noninvasive ventilation during pulmonary rehabilitation in COPD patients]. / Ventilation non invasive au cours de la réhabilitation respiratoire des patients atteints de BPCO.

INTRODUCTION: Pulmonary rehabilitation is currently the gold standard treatment for patients with chronic obstructive pulmonary disease (COPD). However, the workload achieved may be insufficient to obtain physiological benefits because of the restricted respiratory capacity. BACKGROUND: In patients with COPD, changes in flow as well as biomechanical factors (distension) compromise respiratory adaptation to exertion. Some studies have shown that noninvasive ventilation (NIV) during exercise has a positive effect on respiratory muscle workload, physiological parameters and perceived exertion. However the evidence remains insufficient regarding the effects of the NIV during comprehensive pulmonary rehabilitation programs. OBJECTIVES: The identification of criteria which determine responsive patients is necessary in order to reduce human and time costs and to optimize the use of NIV during exercise. CONCLUSIONS: NIV is used during training to overcome dyspnoea and to increase muscle workload. Further studies are needed to verify the effectiveness of NIV in pulmonary rehabilitation.

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

[Domiciliary ventilation in patients with COPD]. / Ventilation à domicile chez les patients atteints de bronchopneumopathie chronique obstructive (BPCO).

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has become one of the main indications for domiciliary ventilation, which is usually non-invasive (NIV). This review focuses on the pathophysiology processes and clinical trial data that underlie current guidelines from international societies. STATE OF THE ART: To date most published studies about domiciliary ventilation in COPD have been short-term and their message is complicated by the presence of significant methodological problems. The two controlled studies of > or =12 months-duration both found that survival was not improved by long-term NIV. Domiciliary ventilation may be considered when long-term oxygen therapy is unsuccessful and when failed with a progressive deterioration in clinical respiratory status with recurrent episodes of acute hypercapnic respiratory failure. A diurnal PaCO(2) > or =55 mmHg (7.3 kPa) is a necessary but not sufficient condition to consider domiciliary ventilation. CONCLUSION: Domiciliary ventilation should only be initiated in selected patients on the basis of clinical symptoms and exacerbation frequency. Until further characterization of patients who are likely to respond, the response to treatment should be assessed regularly.

[Noninvasive ventilation: efficacy of a new ventilatory mode in patients with obesity-hypoventilation syndrome]. / Ventilation non invasive : efficacité d'un nouveau mode ventilatoire chez les patients atteints du syndrome obésité-hypoventilation.

Noninvasive ventilation is recommended to correct the nocturnal hypoventilation and relieve the symptoms of patients with the obesity-hypoventilation syndrome (OHS). The benefits of fixed pressure ventilation (S/T technology) are recognized but limited on account of the variability of nocturnal ventilatory requirements. The new technique AVAPS-AE (automatic EPAP) allows adjustment of the pressure according to the volume currently targeted. Its efficacy has not yet been evaluated. Our objectives are to evaluate firstly, whether AVAPS-AE optimizes the benefits of S/T technology on sleep architecture and quality, secondly, whether these benefits are associated with an improvement in gas exchange, symptoms, exercise tolerance, level of physical activity and quality of life of patients with OHS. In this multicenter trial, 60 newly diagnosed patients with OHS will be randomized to the control (S/T) and trial (AVAPS-AE) groups. A standardized titration procedure will be followed for the calibration of the ventilators. Functional evaluations (polysomnography, blood gases, impedance measurements and walking tests), questionnaires (physical activity, quality of life, quality of sleep and daytime somnolence) visual scales (fatigue, headaches) and a recording of activity will be undertaken after two months of ventilation.

[A comparison of pulmonary rehabilitation delivered in the home or at a centre for patients with COPD]. / Comparaison de la réhabilitation respiratoire de patients atteints de BPCO en centre et à domicile.

AIM: There are few data showing how pulmonary rehabilitation (PR) for COPD patients carried out at home impacts on health-related quality of life (HRQL). The aim of this study was to determine if PR conducted at home improves quality of life. METHODS: We compared the results of home-based PR versus PR performed in an outpatient center. The outcomes were the HRQL measured by the Saint-George's Hospital questionnaire and the 6-minute walk test distance (6MWT). Fifty-six COPD patients were included for PR either at home (n=27) or in the outpatient center (n=29) depending on distance from the center and patients preference. The two groups were similar for sex, age, BMI, lung function, and initial peak oxygen uptake. RESULTS: 6MWT showed a similar non-significant improvement in both groups after PR (+12±46m in home-based PR,+13±34m in outpatient center). HRQL was significantly improved in the home-based group in 2 domains : "Activity" (-8.6±6.4 vs -0.7±17.7, P<0.05), "Impact" (-8.4±6.5 vs 1.6±11.7, P<0.001) and total score (-8.2±4.0 vs 0.0±8.8, P<0.001). CONCLUSION: Pulmonary rehabilitation at home is associated with improvements in health-related quality of life, and thus can be considered where availability of treatment in specialized centers is limited.

Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description.

INTRODUCTION: Obesity is an escalating issue, with an accompanying increase in referrals of patients with obesity-related respiratory failure. Currently, these patients are electively admitted to hospital for initiation of non-invasive ventilation (NIV), but it is unknown whether outpatient initiation is as effective as inpatient set-up. We hypothesise that outpatient set-up using an autotitrating NIV device will be more cost-effective than a nurse-led inpatient titration and set-up. METHODS AND ANALYSIS: We will undertake a multinational, multicentre randomised controlled trial. Participants will be randomised to receive the usual inpatient set-up, which will include nurse-led initiation of NIV or outpatient set-up with an automated NIV device. They will be stratified according to the trial site, gender and previous use of NIV or continuous positive airway pressure. Assuming a 10% dropout rate, a total sample of 82 patients will be required. Cost-effectiveness will be evaluated using standard treatment costs and health service utilisation as well as health-related quality of life measures (severe respiratory insufficiency (SRI) and EuroQol-5 dimensions (EQ-5D)). A change in the SRI questionnaire will be based on the analysis of covariance adjusting for the baseline measurements between the two arms of patients. ETHICS AND DISSEMINATION: This study has been approved by the Westminster National Research Ethics Committee (11/LO/0414) and is the trial registered on the UKCRN portfolio. The trial is planned to start in January 2015 with publication of the trial results in 2017. TRIAL REGISTRATION NUMBER: ISRCTN 51420481.

Determinants of immediate survival among chronic respiratory insufficiency patients admitted to an intensive care unit for acute respiratory failure. A prospective multicenter study. The French Task Group for Acute Respiratory Failure in Chronic Respiratory insufficiency.

In this study, 322 patients were evaluated with two aims: determination of identifiable factors at the time of admission to an ICU that predict short-term survival. Application of the SAPS to this population. Characteristics of patients were as follows: age, 65.5 +/- 14.5 years; COLD, 45 percent; restrictive, 13.4 percent; obstructive and restrictive CRI, 13 percent; asthma progressing to CRI, 11.2 percent; diffuse bronchiectasis, 7.2 percent; neuromuscular diseases, 2.2 percent; others, 8 percent. Cachectic patients, those confined to home, those with initial coma or those who required MV had a higher percentage of M. The SAPS at admission was higher in those patients who died; however, there was no link between the SAPS and M. Prognostic factors in ARF complicating CRI and identifiable at the time of admission to an ICU are few and reflect severity of chronic respiratory disease; SAPS appears to be less useful in ARF complicating CRI.

Survival and long-term follow-up of tracheostomized patients with COPD treated by home mechanical ventilation. A multicenter French study in 259 patients. French Cooperative Study Group.

To define more clearly the value of home mechanical ventilation by tracheostomy (HMVT) in patients with advanced COPD, a retrospective French multicenter study group analyzed the prognostic factors and long-term survival of 259 patients with severe COPD, who were tracheostomized for at least 1 year. Seventy-eight percent of the patients died by the end of the observation period. The actuarial survival rate for the overall study population was, therefore, 70 percent at 2 years, 44 percent at 5 years, and 20 percent at 10 years. These results appear to be better than those of the major published series and compare to the prognosis of COPD patients treated by long-term oxygen therapy (LTO) 15 hr/24 hr. The parameters most closely correlated with a survival for more than 5 years were age < 65 years, use of an uncuffed cannula, and a PaO2 > 55 mm Hg in room air during the 3 months after tracheostomy (p < 0.01). This study, therefore, confirmed the feasibility of HMVT in COPD and should lead to a review of the place of permanent tracheostomy in the long-term prognosis of severe COPD patients.

Nasal mask ventilation in acute respiratory failure. Experience in elderly patients.

Nasal mask ventilation (NMV) has been used successfully in chronic restrictive respiratory failure and more recently in acute exacerbations of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the possible role of NMV in acute respiratory failure (ARF) episodes when mechanical ventilation with endotracheal intubation is questionable. Thirty patients (age, 76 +/- 8.1 years) were treated by NMV during ARF episodes (COPD, 20; other chronic respiratory failure [CRF], 5; chronic heart failure [CHF], 4). All patients were hypoxemic (PaO2, 5.85 +/- 1.62 kPa) and hypercapnic (PaCO2, 8.63 +/- 1.89 kPa) with respiratory acidosis (pH, 7.29 +/- 0.08). In all cases, clinical or physiologic parameters indicated the need for mechanical ventilation, but endotracheal intubation was either not applied because of the age and the physiologic condition of the patients (17 cases) or was postponed (13 cases). NMV was performed using a volume-cycled ventilator and a customized nasal mask. Ventilation was continuous during the first 12 hours and the following nights and was then intermittent during the day. Twenty-one patients improved clinically, within a few hours. Progressive correction of arterial blood gases was observed: PaO2 increased during the first hour, but PaCO2 decreased more slowly. Eighteen patients were able to be successfully weaned from NMV. Twelve patients failed to improve despite NMV: eight of them died and four required endotracheal intubation. There was no difference in the success rate between patients in whom endotracheal ventilation was contraindicated or postponed. Clinical tolerance was satisfactory in 23 patients and poor in seven patients. A return to the respiratory condition was observed in the surviving patients with subsequent discharge from hospital. NMV therefore successfully treated respiratory distress initially in 60 percent of the 30 patients. These results suggest that NMV could be a possible alternative in the treatment of ARF, even in very ill patients, when endotracheal ventilation is controversial or not immediately required.

Long-term efficiency of home nasal mask ventilation in patients with diffuse bronchiectasis and severe chronic respiratory failure: a case-control study.

The aim of this study was to evaluate long-term efficacy and tolerance of nasal mask ventilation (NMV) in a comparative case-control study. Fourteen patients with diffuse bronchiectasis and severe chronic respiratory failure (CRF), treated by long-term oxygen-therapy (LTO) and NMV, were case matched with 14 patients with diffuse bronchiectasis and severe CRF treated with only LTO. Patients and control subjects were compared based on the following parameters: blood gases, FEV1, vital capacity, hospitalizations, and survival. Symptoms, Karnofsky function score, and clinical evolution were also monitored in patients. Three subgroups may be identified according to outcome: two early deaths (subgroup 1), six patients with initial improvement and subsequent deterioration (subgroup 2), and six patients whose conditions remained improved for >2 years (subgroup 3). PaO2 decrease slope was slighter in this last subgroup than subgroup 2. The days of hospitalization were significantly reduced after institution of NMV in the patient group. Comparison between patients and control subjects did not show any difference on PaO2 evolution and on the overall median survival (46 and 40 months in NMV and control group, respectively). Long-term tolerance and compliance remained satisfactory for 11 patients. These results suggest that NMV is feasible as a long-term home treatment in patients with diffuse bronchiectasis. Although our results may have failed to prove a long-term efficiency on the course of blood gases and survival, a beneficial effect is observed with reduction of hospitalizations and improvement of functional status. This study warrants further investigation, in a prospective series, with a larger number of patients.

Nocturnal efficiency and tolerance of a demand oxygen delivery system in COPD patients with nocturnal hypoxemia.

OBJECTIVES: We compared the efficacy of the standard nasal cannula and the demand oxygen delivery system (DODS) during sleep in patients with COPD. SUBJECTS: Twenty patients with moderate or severe COPD were included in the study. METHODS: Four consecutive polysomnographic recordings were performed under the following conditions: DODS powered by compressed air (night 1 [N1]); oxygen delivered with a nasal cannula alone (night 2 [N2]); oxygen delivered through a DODS (night 3 [N3]); and oxygen delivered with nasal cannula alone (night 4 [N4]). Oxygen flow rates with and without DODS were adjusted the day before the first night so that the resulting transcutaneous arterial oxygen saturation (SaO2) was > or = 95%. The following parameters were evaluated each night: apnea-hypopnea index, nocturnal SaO2, total oxygen saving, and several neurophysiologic parameters. RESULTS: The oxygen saving with the DODS was, on average, 60%. All parameters obtained during N2 and N4 (oxygen alone) were identical. The percentage of total recording time spent at SaO2 > or = 95% was comparable between N2 ([mean +/- SD]; 69+/-32%) and N3 (61+/-31%) (difference is not significant [NS]), as was the time spent at SaO2 between 90% and 95% (N2, 29.8+/-31%; N3, 35.9+/-27%; NS) and < 90% (N2, 0.75+/-2.6%; N3, 2.5+/-8.6%; NS). Although the mean response time was not significantly different between N2 and N3, two patients experienced a substantial increase in response time with an SaO2 < 90% on the DODS. The DODS device did not induce any difference in the percentage of time spent in rapid eye movement (REM) sleep (N2, 12.3+/-8.7%; N3, 16.4+/-7.8%; NS) or non-REM sleep (N2, 87.7+/-8.7%; N3, 83.7+/-7.9%; NS). Non-REM distribution in stage 1-2 sleep and in stage 3-4 sleep was comparable between N2 and N3. Similarly, no difference was observed for the sleep efficiency index (N2, 71+/-15%; N3, 69.6+/-14%; NS). Differences between sleep onset latency times were NS. CONCLUSIONS: In a majority of moderate to severe COPD patients, the use of a DODS device does not induce any significant alteration of nocturnal neurophysiologic and ventilatory profiles. However, the presence of nocturnal desaturation in a few patients justifies the need to systematically perform a ventilatory polygraphic recording when prescribing a DODS device.

Effects of repeated administration of zolpidem on sleep, diurnal and nocturnal respiratory function, vigilance, and physical performance in patients with COPD.

STUDY OBJECTIVE: To assess the effects of repeated 10-mg oral doses of zolpidem on diurnal and nocturnal respiratory function, as well as on diurnal vigilance and physical performance in COPD patients with disordered sleep. DESIGN: Prospective single-blind placebo-controlled clinical study. SETTING: Outpatients of a respiratory medicine department. PATIENTS AND METHODS: Patients with stable COPD were enrolled for 10 days (D0 to D10), ie, 9 consecutive nights (N1 to N9). They received placebo on N1 and N9 and zolpidem, 10 mg, from N2 to N8. MEASUREMENTS: The following parameters were measured: nocturnal polysomnographic recordings with respiratory signals and arterial blood gas values on retiring and awakening on N0, N1, N2, N8, and N9; subjective evaluation of the quality of sleep and of diurnal vigilance by visual analog scales every day from D0 to D10; pulmonary function test, central control of breathing, and walking test on D0 and D9; biological laboratory tests and theophylline level on D0 and D8. RESULTS: Ten COPD patients (PaO2 = 72.7 +/- 7.6 mm Hg; PaCO2 = 47.7 +/- 5.4 mm Hg; FEV1 = 0.84 +/- 0.3 L; FEV1/vital capacity = 42.5 +/- 12.3%), 56.8 +/- 8.3 years old, were studied. Compared with placebo, no significant change was found for the various sleep architecture parameters, except an increase in the duration of stage 2 during the D8/N8 night (p < 0.05). In contrast, the autoevaluation score for the quality of sleep was significantly improved during the D6/N6 night relative to that with placebo (p < 0.05), with no change in the other subjective criteria. No variable of the nocturnal respiratory parameters, pulmonary function test, central control of breathing, and physical performance was altered by zolpidem. Arterial blood gas values on awakening were not altered. Clinical and biological tolerance of zolpidem was correct with no significant variation of the theophylline level. CONCLUSION: This study shows that repeated 10-mg oral doses of zolpidem during 8 days does not impair nocturnal respiratory and sleep architecture parameters or diurnal pulmonary function tests, central control of breathing, and physical performances in patients with stable COPD.

Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis.

STUDY OBJECTIVES: Bronchiectasis has been reported in a few patients with homozygous alpha(1)-antitrypsin (AAT) deficiency, but the distribution of AAT alleles among bronchiectatic patients is not known. PATIENTS AND DESIGN: Two hundred two patients, 104 men and 98 women, with a mean age (SD) of 63.7 +/- 15.4 years, had bronchiectasis diagnosed by CT scan alone (n = 178), bronchography with or without CT scan (n = 17), or radiography alone (n = 7). AAT phenotypes (classified according to the protease inhibitor [PI] system) were determined by isoelectric focusing in blood samples obtained from all patients. Bronchiectasis was primary in 121 cases and secondary in 81 patients. Allele and phenotype frequencies were compared retrospectively between bronchiectatic patients and healthy blood donors living in the same geographic area. RESULTS: The PI phenotype frequencies among patients were the following: MM, 81.18%; MS, 11.88%; MZ, 3.46%; IZ, 0.49%; IM, 0.49%; SS, 1.48%; SZ, 0.49%; and ZZ, 0.49%. The allelic frequencies among patients were the following: M, 89.1%; S, 7.67%; Z, 2.72%; and I, 0.49%. There was no difference in the distribution of alleles or phenotypes either between patients and control subjects or between patients with secondary and primary bronchiectasis. A significant difference was found between bronchiectatic patients with and without coexisting emphysema (p = 0.028). This difference was caused by an overrepresentation of PI*Z alleles in bronchiectatic patients with coexisting emphysema. CONCLUSIONS: Our results do not support a physiopathologic implication of the AAT genes in the development of bronchiectasis. We suggest that bronchiectasis may be a consequence of emphysema in PI*Z patients rather than a primary effect.

Once-daily oral gatifloxacin vs three-times-daily co-amoxiclav in the treatment of patients with community-acquired pneumonia.

A double-blind, double-dummy, multicentre, multinational, parallel-group study was designed to establish proof of equivalence between oral gatifloxacin and oral co-amoxiclav in the treatment of 462 patients with mild-to-moderate community-acquired pneumonia. Eligible patients were randomised equally to either gatifloxacin 400 mg once-daily plus matching placebo for 5-10 days, or amoxycillin 500 mg + clavulanic acid 125 mg three-times-daily for 5-10 days. The primary efficacy endpoint was clinical response (clinical cure plus improvement) at the end of treatment. Overall, a successful clinical response was achieved in 86.8% of gatifloxacin-treated patients, compared with 81.6% of those receiving co-amoxiclav, while corresponding rates of bacteriological efficacy (eradication plus presumed eradication) were 83.1% and 78.7%, respectively. The safety and tolerability profile of gatifloxacin was comparable to that of co-amoxiclav, with adverse gastrointestinal events, e.g., diarrhoea and nausea, being the most common treatment-related adverse events in both groups. The study showed no evidence of gatifloxacin-induced phototoxicity, musculoskeletal disorders, or hepatic and renal problems. Overall, this study showed that gatifloxacin was equivalent clinically to a standard course of co-amoxiclav in patients with community-acquired pneumonia, and that gatifloxacin was safe and well-tolerated.

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk).

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.