The clinical and integrated management of COPD.

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2<88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe or "very severe COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneusly published in Multidisciplinary Respiratory Medicine 2014; 9:25.

Endometrial expression of leptin receptor and members of the growth hormone-Insulin-like growth factor system throughout the estrous cycle in heifers.

The growth hormone (GH)-insulin-like growth factor (IGF) system is expressed in bovine uterus during the estrous cycle and early pregnancy and is acknowledged to play an important role in regulating the development of the embryo and uterus. The leptin receptor (LEPR) is also expressed in the bovine uterus although it is not known whether its expression varies during the estrous cycle. In this study, the expression of the IGF-I and -II, the type 1 IGF receptor (IGF-1R), GH receptor (GHR) and LEPR transcripts was determined on endometrial transcervical biopsies collected on days 0 (estrus), 5, 12 and 19 of the cow estrous cycle (n=8). The expression of mRNA was determined by RT real time PCR using ribosomal protein L19 as a housekeeping gene. It has been demonstrated for the first time that LEPR mRNA is expressed in the bovine uterus throughout the estrous cycle and that it presents a cycle-dependent variation, with higher levels observed during the luteal phase. The expression of IGF-I mRNA was greatest at estrus and day 5 (100%), and decreased on days 12 and 19 to 47% and 35% of the initial values. IGF-II mRNA increased on day 12 and decreased sharply thereafter (to one-third of day 12 values). Interestingly, IGF-1R showed the same pattern as IGF-II: increased 50% on day 12 compared to values at estrus and presented a sharp decrease on day 19. The expression of GHR transcript was greatest at estrus and on day 5 and progressively decreased thereafter. These results show that the GH-IGF system components are distinctively regulated during the estrous cycle suggesting that modulation of the IGF system may influence uterine activity during this period. The increase in the uterine sensitivity to IGFs during the late luteal phase - as demonstrated by the increased IGF-1R expression - concomitant with the increased IGF-II mRNA expression may reinforce the role of IGF-II during early pregnancy. Moreover, leptin is also likely to play roles during early embryo development.

Standards of care and clinical predictors in patients hospitalised for a COPD exacerbation--the Italian SOS (Stratification Observational Study).

BACKGROUND AND AIMS: Hospitalisations for chronic obstructive pulmonary disease (COPD) exacerbations are major events in the natural history of the disease in terms of survival, quality of life and risk of further episodes of exacerbation. The aims of study were to evaluate: 1. adherence to recommended standards of care; and 2. clinical factors influencing major outcomes during hospitalisation for an episode of COPD exacerbation and within a 6-month follow-up. METHODS: An observational, prospective study was conducted in 68 centres. Assessment of standards of care included diagnostic procedures (such as pulmonary function tests and microbiology) and management options (such as drug therapies, vaccinations and rehabilitation). Outcome measures relevant to the hospitalisation were: survival, need for mechanical ventilation, and length of stay (LOS). Outcomes at 6-months were: survival, exacerbations and hospitalisations for an exacerbation. Multivariate logistic regression was applied to evaluate the relation between clinical factors and outcomes. RESULTS: 931 patients were enrolled. Only 556 patients (59.7%) were diagnosed COPD and stratified for severity with the support of spirometry (FEV1/VC < or = 0.7) and were considered for outcome analysis. Among treatments, pulmonary rehabilitation and anti-smoking counselling were applied infrequently (14.5 and 8.1% of patients, respectively). Within six months 63 COPD patients (17.7%) had at least one episode of exacerbation prompting a further hospitalisation and 19 died (5.3%). Predictor of mortality was the co-morbidity Charlson index (odds ratio, OR 10.3, p=0.03 CI: 1.25-84.96). A further hospitalisation was predicted by hospitalisation for an exacerbation in the previous 12 months (OR 3.59, p=0.003 CI: 1.54-8.39). CONCLUSIONS: Standards of care were far lower than recommended, in particular 40% of patients were labelled as COPD without spirometry. COPD patients with a second hospitalisation in 12 months for an exacerbation had about 3 times the risk of suffering a new episode and hospitalisation in the following six months.

Nocturnal oxygen desaturation correlates with glycemia levels in patients with coronary artery disease.

AIM: Sleep-disordered breathing (SDB) has a high occurrence in patients with coronary artery disease. The aim of the present study was to examine the relationships between the overnight oxygen desaturation index (ODI) and metabolic and anthropometric parameters in a sample of patients who underwent percutaneous transluminal coronary angioplasty (PTCA). METHODS: The overnight pulse-oximetry recording ODI (desaturation >4%, length >10 s/events per hour) was performed in 29 patients with coronary heart disease, after they underwent PTCA. All study participants performed dynamic spirometric test, echocardiography, anthropometric measurements, bio impedance analysis. Fasting blood sample was collected to measure metabolic parameters. Using ODI category, the patients were grouped as follows: group N, N.=9 (ODI= or <5 events/hour); group A, N.=14 (515 events/hour). RESULTS: Among the studied patients, 69% had a nocturnal ODI>5 and 48% had a nocturnal ODI between 5 and 15 events/hour. ODI values were correlated with body mass index (BMI) (P<0.05) but not with waist to hip ratio, or percent body fat. After adjustment for BMI values, there was a significant positive correlation of ODI values with fasting glucose serum levels (P<0.05). CONCLUSION: These data suggest that early metabolic dysfunction may occur with SDB before overt clinical manifestation of underlying disease in patients with preobesity and ischemic heart disease. Patients with ischemic heart disease should be screened for SDB by ODI, also according to fasting glucose levels.

GOLD severity stratification and risk of hospitalisation for COPD exacerbations.

BACKGROUND AND AIM: The Italian Costs for Exacerbations in COPD ("ICE") study, following a pharmacoeconomic assessment of costs due to COPD exacerbations (primary endpoint), aimed also at evaluating (secondary endpoint) which clinical factors, among those considered for cost-analysis, may, at follow up, present a risk of new exacerbations and re-admission to hospital. MATERIALS AND METHODS: A prospective, multicentre study was carried out on COPD patients admitted to 25 Hospital Centres as a result of an exacerbation from October-December 2002. Following discharge, a 6-month follow-up was performed in each patient via three bi-monthly telephone interviews with a questionnaire administered by an investigator clinician. RESULTS: 570 patients were eligible for data processing, mean age 70.6 years (+/- 9.5 standard deviation, SD), males 69.2%. According to GOLD, severity stratification was as follows: moderate 36.4%; severe 31.3%; very severe 32.3%. 282 patients experienced at least one exacerbation at follow up, 42% of exacerbations requiring hospitalisation. No significant association was seen between exacerbations and GOLD stage or co-morbidities or treatments except LTOT. Conversely, COPD functional severity influenced hospitalisations very significantly, with relative risks 2.6 (95% Confidence Interval, CI 1.8-3.8) and 2.0 (CI 1.3-2.8) (GOLD very severe versus moderate and severe, respectively), and 1.3 (CI 0.85-2.1) (GOLD severe versus moderate). Hospitalisations were also significantly associated with treatments denoting more severe conditions (oral corticosteroids, oral theophylline, and LTOT). CONCLUSIONS: Severity stratification of COPD patients according to respiratory function classes as outlined in GOLD guidelines and need for LTOT are confirmed as important predictors of hospitalisation for an exacerbation.

GP management of community-acquired pneumonia in Italy: the ISOCAP study.

BACKGROUND: Community-Acquired Pneumonia (CAP) is still a significant problem in terms of incidence, mortality rate, particularly in infants and the elderly, and socioeconomic burden. General Practitioners (GPs) are the first reference for patients with this disease, but there are few published studies regarding the outpatient treatment of CAP. METHODS: The ISOCAP study aimed to identify the type and outcome of the diagnostic-therapeutic management of CAP by GPs in Italy, within the framework of developing a closer interrelationship between GPs and pulmonary specialists. Thirty-six Pulmonary Divisions throughout Italy each contacted 5 local GPs who agreed to recruit the first 5 consecutive patients who consulted them for suspected CAP within the study's 1-year observation period. RESULTS: A total of 183 GPs took part in the study and enrolled, by the end of the observation period, 763 CAP patients; of these, complete data was available for 737 patients [males=373, females=364, mean age (+/- SD) 58.8 +/- 19.6 years]. 64.4% of patients had concomitant diseases, mainly systemic arterial hypertension and COPD. Diagnosis of CAP was based by GPs on physical examination only in 41.6% of cases; in the remaining chest X-ray was also performed. In only 4.6% of patients were samples sent for microbiological analysis. All patients were treated with antibiotics: 76.7% in mono-therapy, 23.3% with a combination of antibiotics. The antibiotic class most prevalently used in mono-therapy was cephalosporin, primarily ceftriaxone; the most frequently used combinations were cephalosporin + macrolide and cephalosporin + quinolone. Mono-therapy was effective in 70% of cases, the combination of two or more antibiotics in 91.2% of patients. Overall treatment efficacy was 94.7%; hospitalisation was required in 8.5% of cases. CONCLUSIONS: Outpatient management of CAP by GPs in Italy is effective, hospitalisation being necessary only in the most severe cases due to age, co-morbidities or extent of pneumonia. This signifies a very significant savings in national health costs.

Adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma symptom control at a lower dose than fixed maintenance dosing.

Asthma guidelines suggest a stepwise approach to maintenance pharmacological treatment of persistent asthma until control is attained, and a 3 month review of the fixed maintenance dosing for step-up or step-down adjustment. This 12-week study compared the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler 160/4.5 or 80/4.5 microg) given as adjustable maintenance or fixed maintenance dosing. Patients (n = 2358) were randomised to budesonide/formoterol fixed maintenance dosing (two inhalations bid) or adjustable maintenance dosing (two inhalation bid; stepping up to four inhalations bid if asthma worsened for a maximum of 14 days; stepping down to two inhalations once nocte or one inhalation bid if symptoms were controlled) for 12 weeks, following a 4-week run-in period on budesonide/formoterol two inhalations bid. Primary efficacy variables were frequency of asthma exacerbations and changes in patients' asthma symptom severity. Secondary variables were asthma control, safety and health economics. Both adjustable maintenance dosing and fixed maintenance dosing were associated with similar low frequency of exacerbations (5% both groups; ns) and similarly improved lung function, with similarly fewer nocturnal awakenings and less asthma symptoms compared with the mean value of the run-in period. However, patients on adjustable maintenance dosing used 24% fewer study drug compared with fixed maintenance dosing (2.95 versus 3.86 inhalations daily; p < 0.0001) and incurred in a significant (p <0.0001) reduction in total costs (direct+indirect) compared with fixed maintenance dosing. In conclusion, adjustable maintenance dosing with budesonide/formoterol effectively controls asthma at a reduced drug load with lower costs than fixed maintenance dosing.

Pulmonary artery leiomyosarcoma with thyroid metastases.

Primary pulmonary artery sarcomas are uncommon and usually fatal tumours. The diagnosis of these tumours is delayed in most cases as they are mistaken for pulmonary thromboembolism. We present a fatal case of a woman referred to us five months after a primary diagnosis of pulmonary thromboembolism, due to an increase in dyspnea and presence of hemoptysis despite having undergone anticoagulant treatment. On the basis of the findings obtained by computed tomography, echocardiogram and MRI, a mass arising from the pulmonary trunk was evidenced, that suggested other diagnostic hypotheses. The worsening of patient's conditions did not allow an endovascular catheter biopsy and diagnosis was made at autopsy. The mass was a leiomyosarcoma of the pulmonary artery with thyroid metastases, which is an uncommon findings.

EDU-CARE, a randomised, multicentre, parallel group study on education and quality of life in COPD.

Chronic obstructive pulmonary disease (COPD) represents one of the main causes of morbidity and mortality in the western world. Unfortunately, its therapy is largely palliative, the key aims of treatment being to reduce exacerbations, minimise symptoms, and improve patients' ability to perform their usual daily activities. In the absence of true disease-modifying treatments, the concept of rehabilitation has become important. In addition, it has been shown that educational and self-management programmes may play a role in the general treatment of COPD patients. This study was promoted by the Italian Association of Hospital Pulmonologists (AIPO) with the aim to verify changes and improvements induced by an educational programme validated by AIPO in patients with COPD. Edu-Care is a 6-month, multicentre, randomised, controlled, parallel-group study. In addition to treatment within the usual therapeutic schemes for COPD, patients were randomised to either the 'Educational' group, i.e. to receive a formal and structured educational programme, or the 'Normal General Advice' group, i.e. to receive the usual general advice given by general practitioners on life-style and on the disease's risk factors and treatment. A number of evaluations were performed: pulmonary function test, walking distance, quality of life, locus of control, register of number of exacerbations and hospital admissions. To date, of the 1,230 patients enrolled interim data are available from 1,003 patients. Males represent 85% of the study population. Smoking habit is quite a common status (21%). In the year prior to enrolment 34% of patients had one exacerbation, 49% 2-3 exacerbations, and 17% more than 3 exacerbations. Seventy-two percent of patients were not hospitalised over the year prior to enroLlment, while 22% were hospitalised once and 6% had more than 2 hospitalisations. Edu-Care is the first large study aimed to evaluate the efficacy of an educational programme for patients with COPD. AIPO wishes to make a contribution to this important field. This is the reason why Edu-Care includes a very large number of patients in numerous Italian centres throughout northern and southern Italy.

An observational study on the epidemiology of respiratory tract bacterial pathogens and their susceptibility to four injectable beta-lactam antibiotics: piperacillin, piperacillin/tazobactam, ceftazidime and ceftriaxone.

Bacterial infections of the respiratory tract account for a large proportion of total medical consultations in general practice. In recent years, antibiotic resistance has increased alarmingly in a number of bacterial species that are common causes of these infections. The aim of this observational study was to determine the antibiotic resistance of microbial agents isolated from patients with acute or acutely exacerbated respiratory infections. Subjects recruited as potential sources of bacteria were either outpatients seen in a number of specialized clinics and hospital practices, or hospitalized patients. Overall, 648 consecutive patients (67% male, mean age 48.1+/-27.0 years) with infection of the upper or lower respiratory tract were observed during a 13-month period. A total of 551 pathogenic microbial strains were isolated and tested for their in vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and ceftriaxone. Among all isolates, the four most frequent pathogens were Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates, 18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46 isolates, 8%). The susceptibility of gram-positive isolates ranged from 97.5% to 95.1%, and no remarkable difference was found in the antibacterial activity of tested b-lactam antibiotics. The susceptibility of gram-negative isolates to piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%, respectively. In contrast, differences were found between piperacillin (or piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone (p<0.0003) in gram-negative isolates. We conclude that, despite the extensive use of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in medical practice during the past three decades, the susceptibility of the most common pathogens involved in the etiology of upper and lower respiratory tract infections to these antibiotics is still high. In particular, bacterial resistance developed by gram-positive organisms against piperacillin is negligible and not alarming.

A comparative study of clarithromycin modified release and amoxicillin/clavulanic acid in the treatment of acute exacerbation of chronic bronchitis.

This phase III, investigator-blind, randomized, parallel-group study compared the efficacy and tolerability of clarithromycin modified release (MR) with those of amoxicillin/clavulanic acid in 250 adult outpatients with acute exacerbationof chronic bronchitis (AECB). Patients received either clarithromycin MR 500 mg once daily or amoxicillin/clavulanic acid 500 mg/125 mg three times daily for 7 days. Primary endpoints were sponsor-defined clinical response and pathogen outcome at the end of treatment. Secondary endpoints were sponsor-defined clinical response and pathogen outcome at study end, investigator-defined clinical response at end of treatment and end of study, resolution or improvement of signs and symptoms, eradication of baseline pathogens, serologic outcome for atypical pathogens, and occurrence of reinfection and superinfection. Adverse events and compliance were also evaluated. Clinical and bacteriologic outcomes with both treatments for all endpoints were statistically equivalent, as were total adverse events, although the incidences of digestive disturbances (13% vs 4%) and discontinuations due to adverse events (8 vs 2 patients; P < or =.05) were significantly higher with amoxicillin/clavulanic acid. Ninety-five percent of patients receiving clarithromycin MR and 80% receiving amoxicillin/clavulanic acid were 100% compliant with medication (P < or =.05). Clarithromycin MR and amoxicillin/clavulanic acid are both well tolerated and effective as therapy for AECB; however, clarithromycin produced fewer side effects and discontinuations and higher compliance rates.

Bacterial agents of lower respiratory tract infections (LRTIs), beta-lactamase production, and resistance to antibiotics in elderly people. DEDALO Study Group.

This study determined the etiology of lower respiratory tract infections in the elderly and assessed whether the growth of beta-lactamase producing bacteria is particularly favoured in these patients. Between December 1998 and May 1999, 187 patients with community-acquired pneumonia (CAP), and 887 patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were enrolled. The mean age was 74 years (range of 65-94 year). Sputum and bronchial aspirate for microbiological investigation were obtained. Besides organisms commonly involved in bacterial infections of the lower respiratory tract (i.e. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), Enterobacteriaceae and Pseudomonas spp. were also found. A high percentage of these bacteria were beta-lactamase producers. These data along with the clinical presentation, severity of infection, and epidemiological knowledge, might represent a guide for the choice of empiric antimicrobial treatment.

Neurofilament mRNAs are present and translated in the normal and severed sciatic nerve.

Local protein synthesis within axons has been studied on a limited scale. In the present study, several techniques were used to investigate this synthesis in sciatic nerve, and to show that it increases after damage to the axon. Neurofilament (NF) mRNAs were probed by RT-PCR, Northern blot and in situ hybridization in axons of intact rat sciatic nerve, and in proximal or distal stumps after sciatic nerve transection. RT-PCR demonstrated the presence of NF-L, NF-M and NF-H mRNAs in intact sciatic nerve, as well as in proximal and distal stumps of severed nerves. Northern blot analysis of severed nerve detected NF-L and NF-M, but not NF-H. This technique did not detect the three NFs mRNAs in intact nerve. Detection of NF-L and NF-M mRNA in injured nerve, however, indicated that there was an up-regulation in response to nerve injury. In situ hybridization showed that NF-L mRNA was localized in the Schwann cell perinuclear area, in the myelin sheath, and at the boundary between myelin sheath and cortical axoplasm. RNA and protein synthesizing activities were always greater in proximal as compared to distal stumps. NF triplet proteins were also shown to be synthesized de novo in the proximal stump. The detection of neurofilament mRNAs in nerves, their possible upregulation during injury and the synthesis of neurofilament protein triplet in the proximal stumps, suggest that these mRNAs may be involved in nerve regeneration, providing a novel point of view of this phenomenon.

Validation of a new technique to assess exhaled hydrogen peroxide: results from normals and COPD patients.

Chronic airways inflammation in chronic obstructive pulmonary disease (COPD) induces the activation of several cell types with delivery of proteases and reactive oxygen species (ROS). Assessing oxidant content in the exhaled air of COPD patients has proven useful in monitoring airway inflammation. The present study was designed to confirm the usefulness of exhaled hydrogen peroxide concentration determination in COPD patients using a new technique which allows longer storage of the expired air condensate before the H2O2 assay. The technique was applied in 13 healthy nonsmoking subjects (six male, age range 22-40 yrs) and in seven patients (five male, age range 58-81 yrs) with mild or moderate COPD. Subjects breathed into a one-valve mouthpiece, and the exhaled air was directed into a vial kept at 0 degree C. After approximately 15 min of quiet breathing, 1 mL of expired air condensate was collected. An aliquot, 450 microL, of this sample was immediately added to an equal volume of a reaction mixture containing 2 mM 3,5,3',5'-tetramethylbenzidine and 40 microL of enzyme stock solution (0.5 mg.mL-1). After 15 min, 45 microL sulphuric acid was added (1 N final concentration), resulting in a reaction mixture pH of 1.0. After a further 10-min incubation, H2O2 concentration determination was performed spectrophotometrically at 450 nm. This solution, as well as the H2O2 assay, was stable for > or = 24 h if the sample was kept in the dark and at 4 degrees C. There was high stability on repeated measures, with a coefficient of variation equal to zero. The mean +/- SD H2O2 level in exhaled air from normal subjects was 0.12 +/- 0.09 microM, whereas it was significantly increased in COPD patients (0.50 +/- 0.11 microM; p = 0.0001 compared to healthy subjects). In three healthy control subjects, a normal H2O2 level in expired air increased to 0.70-0.80 microM during an acute upper respiratory tract infection. This new technique of hydrogen peroxide assay in expired air condensate greatly minimizes the inaccuracy deriving from the instability of hydrogen peroxide. The preliminary results obtained using this technique provide direct evidence for increased reactive oxygen species production in the airways of stable chronic obstructive pulmonary disease patients. However, the specificity of the procedure could be reduced by the interference of upper respiratory tract infections.

Effect of intravenous fructose 1,6-diphosphate administration in malnourished chronic obstructive pulmonary disease patients with chronic respiratory failure.

BACKGROUND: Weight loss and skeletal muscle wasting are common in patients with chronic obstructive pulmonary disease (COPD) and can influence the course and the prognosis of COPD. Hypophosphatemia is a pathologic status often characterized by muscle weakness and is a frequent laboratory finding in these patients. OBJECTIVE: The aim of the present study was to evaluate the effect of an organic phosphate (fructose 1,6-diphosphate, FDP) administration on respiratory performance in 45 malnourished COPD patients in stable clinical conditions. METHODS: Physiologic evaluation including spirometry, maximal voluntary ventilation (MMV), elevated arm test, maximal mouth pressures (PImax and PEmax), respiratory response to CO(2), oxygen (PaO(2)) and carbon dioxide (PaCO(2)) arterial tension, a visual analogic scale (VAS) to measure dyspnea, and complete blood tests were done at the beginning and again at the end of the study. RESULTS: After FDP administration, there was a significant increase in PImax (43.0 +/- 18.3 cm H(2)O before treatment vs. 49.8 +/- 14.9 cm H(2)O after treatment; p < 0.005). This did not occur in the placebo group (40.3 +/- 17.4 cm H(2)O before treatment vs. 42.6 +/- 20.1 cm H(2)O after treatment, nonsignificant). There was also a trend of VAS to decrease and of MVV to increase. CONCLUSIONS: These results show that FDP administration may be useful in the management of malnourished COPD patients, especially in increasing their respiratory muscle strength.

New therapeutic approach to persistent asthma.

The goal of asthma treatment has moved from achieving symptom relief alone to overall disease control. The latest guidelines propose that first-line treatment of mild persistent asthma requires the introduction of anti-inflammatory agents, preferably inhaled corticosteroids at low dose. In patients in whom control of disease is not achieved with this treatment, it was demonstrated that addition of a long-acting beta 2-agonist is more effective than increasing the dose of inhaled corticosteroid. Addition of a long-acting beta 2-agonist to an inhaled corticosteroid not only improves symptoms and lung function but also reduces the risk of asthma exacerbations, suggesting complementary therapeutic activity. Therefore, use of long-acting bronchodilators with inhaled corticosteroids is a prerequisite for optimal management of the disease. For this reason, the logical development in asthma management would be a combination of these two classes of drug in a single inhaled formulation. Fixed combinations of the long-acting beta 2-agonist salmeterol and the inhaled corticosteroid fluticasone propionate were launched recently. Results from recent clinical trials have demonstrated that the combination of salmeterol and fluticasone propionate improves control of asthma in the majority of patients with moderate-to-severe asthma and enhances compliance by virtue of both drugs being in the one inhaler. The possibility to treat asthma of differing severity is provided by the flexibility to choose between three different doses of fluticasone propionate in the fixed combination devices. Another obvious advantage of the combination is cost savings, as the fixed combination inhaler is cheaper than giving the two drugs separately. The introduction of combination preparations is an important step forward in asthma management, which is expected to be a popular choice with both patients and physicians.

N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD.

OBJECTIVE: This study was performed to confirm the efficacy of a 6-month therapy with a formulation of N-acetylcysteine (NAC; 600 mg/day p.o.) on frequency and severity of exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). METHODS: One hundred sixty-nine patients attending five Italian centres were recruited in an open, randomized, controlled study. The patients were randomly allocated to standard therapy plus NAC 600 mg once a day or standard therapy alone over a 6-month period. At baseline, medical history was evaluated, and physical examination was performed; occurrence and severity of exacerbations and side effects of NAC were analyzed after 3 and 6 months. RESULTS: The results showed a decreased number of exacerbations (by 41%) in the group of patients treated with NAC and standard treatment: 46 patients had at least one exacerbation as compared with 63 patients of the group treated with standard therapy alone. Also the number of the patients with two or more exacerbations was lower in the NAC group (26%) than in the standard-therapy group (49%). The number of sick days was less (82) in the NAC group as compared with the standard-therapy group (155). There was a small but significant improvement in FEV(1) and MEF(50) in the NAC group. NAC once a day was well tolerated. There were no differences in the number of side effects reported in both groups. CONCLUSIONS: These data confirm results of previous studies which reported a reduction in the number of exacerbations in patients having moderate to severe COPD treated with the antioxidant NAC. Further, the once-daily formulation is well tolerated and is likely to improve patient compliance with the prescribed regimen.