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COPD is a leading cause of morbidity and mortality worldwide. Long-term cigarette smoking is the cause of > 90% of COPD cases in Westernized countries. However, only a fraction of chronic heavy smokers develop symptomatic COPD by age 80. COPD is characterized by an abnormal immune response in the lower airways, and its progression is associated with infiltration of the lung by innate and adaptive inflammatory immune cells that form lymphoid follicles. There is growing evidence that both cellular- and antibody-mediated autoimmunity has a fundamental role in the pathogenesis of stable COPD. In particular, carbonyl-modified proteins may help to drive autoimmunity in COPD and cause the characteristic small airways abnormalities and even contribute to the pathogenesis of pulmonary emphysema. Although direct, indirect, and circumstantial evidence of a role for autoimmunity in stable patients with COPD has been identified, no cause-and-effect relationship between autoimmunity and the mechanisms of COPD has been firmly established in man. As such, the potential contribution of an autoimmune response to the pathogenesis of COPD exacerbation is still being investigated and represents an area of active research. Many drugs targeting autoimmune responses are already available, and the results of controlled clinical trials are awaited with great interest. The potential for measuring specific serum autoantibodies as biomarkers to predict clinical phenotypes or progression of stable COPD is promising., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD., Methods: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis., Results: TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, in patients with stable COPD compared with control smokers with normal lung function. TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and smokers with mild/moderate stable COPD compared with control nonsmokers and correlated significantly with pack-years of smoking. However, TGF-β3 + cells decreased in patients with severe/very severe COPD compared with control smokers. Latent TGF-β binding protein 1 expression was increased in the bronchial lamina propria in subjects with stable COPD of all severities compared with control smokers with normal lung function. Bone morphogenetic protein and activin membrane-bound inhibitor expression (BAMBI) in the bronchial mucosa was significantly increased in patients with stable COPD of all severities compared with control subjects. No other significant differences were observed between groups for all the other molecules studied in the bronchial mucosa and peripheral lung., Conclusions: Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD. Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

We present here the case of a 30-year-old man with a long term history of nephrotic syndrome (NS) who developed an episode of acute left main pulmonary artery thrombosis complicated by a lung abscess. During the hospital admission was also identified a concomitant hyperhomocysteinemia. After an atypical resection of the left upper pulmonary lobe and the starting of long term anticoagulation the patient was discharged but did not attend the planned follow up visits until one year later when he was seen again for severe dyspnea and exercise intolerance. At this time chronic thromboembolic pulmonary hypertension (CTEPH) was diagnosed by lung perfusion scintigraphy and right heart catheterization. He initially refused the surgical treatment but, after six months, for the presence of worsening dyspnea was referred for bilateral pulmonary endarterectomy followed by a cardio-thoracic rehabilitation program. After a follow-up of seven years the patient is alive and in stable conditions. NS and hyperhomocysteinemia are both known risk factors for pulmonary embolism (PE), but their association with CTEPH is extremely rare. We discuss here the possible mechanisms linking these conditions. CTEPH must be suspected in any patient with NS, with or without hyperhomocysteinemia, and unexplained dyspnea.

Introduction: Current national and international guidelines for the management of patients with stable chronic obstructive pulmonary disease (COPD) recommend the use of inhaled long-acting bronchodilators, inhaled glucocorticoids and their combinations for maintenance treatment of moderate to severe stable COPD. Areas covered: The role of fluticasone furoate (FF) and vilanterol (VI) once daily combination therapy for the regular treatment of patients with stable COPD is discussed in this review. Expert commentary: The regular treatment of moderate to severe stable COPD with once daily FF/VI combination therapy is effective, as seen in in several large placebo-controlled clinical trials involving many thousands of patients. FF/VI improved lung function, decreased respiratory symptoms and decreased the number of COPD exacerbations, including COPD-related hospitalizations. FF/VI combination therapy has also been approved for this indication in most countries. The use of this combination therapy may significantly decrease the economic costs for some National Health Services.

Background: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources., Aim: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting., Method: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society., Results: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients)., Conclusions: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The role of disability and its association with patient-reported outcomes in the nonsevere forms of chronic obstructive pulmonary disease (COPD) has never been explored., Objectives: The aim of this study was to assess, in a cross-sectional real-life study, the prevalence and degree of disability in moderate COPD patients and to assess its association with health status, illness perception, risk of death and well-being., Methods: Moderate COPD outpatients attending scheduled visits were involved in a quantitative research program using a questionnaire-based data collection method., Results: Out of 694 patients, 17.4% were classified as disabled and 47.6% reported the loss of at least one relevant function of daily living. Disabled patients did not differ from nondisabled patients in terms of working status (p = 0.06), smoking habits (p = 0.134) and ongoing treatment (p = 0.823); however, the former showed a significantly higher disease burden as measured by illness perception, health status and well-being. The stepwise regression analysis showed that the modified Medical Research Council (mMRC) score was the most relevant factor related to COPD disability (F = 38.248; p = 0.001). Patient stratification was possible according to the forced expiratory volume in 1 s (FEV1) value and an mMRC score ≥2, which identified disabled patients, whereas the mMRC values were differently associated with the risk of disability., Conclusion: A significant proportion of individuals with moderate COPD reported a limitation of daily life functions, with dyspnea being the most relevant factor inducing disability. Adding the evaluation of patient-reported outcomes to lung function assessment could facilitate the identification of disabled patients., (© 2015 S. Karger AG, Basel.)

We present a case of fatal pneumomediastinum in a patient with acute respiratory failure caused by acute exacerbated chronic obstructive pulmonary disease (AECOPD) and interstitial lung disease (ILD) precipitated by noninvasive mechanical ventilation (NIMV). To our knowledge, this is the first case reported in the literature. NIMV is very useful to treat acute respiratory failure due to AECOPD improving survival and avoiding endotracheal intubation. Use of NIMV in end stage ILD is not standardized and efficacy is to be proven. No data are reported to manage patient with concomitant COPD and ILD. Pathophysiological mechanisms underlying this fatal complication are explained and suggestions to treat this subgroup of patients discussed.

Background: While the effects of postural change on arterial oxygenation have been well documented in normal subjects, and attributed to the relationship of closing volume (CV) to the tidal volume, in liver cirrhosis such postural changes have been evaluated mainly in a rare, peculiar clinical end-stage condition which is characterized by increased dyspnea shifting from supine to upright position ("platypnea"). The latter is associated with worsening of PaO2 ("orthodeoxia"). We evaluated the effects of postural changes on arterial oxygenation in patients affected by mild/moderate liver cirrhosis., Methods: We performed pulmonary function tests and arterial blood gas evaluation in sitting and supine positions in 22 patients with mild/moderate liver cirrhosis, biopsy-proved, and 22 matched non-smokers control subjects., Results: Recumbency elicited a decrease of PaO2 (Δ(sup-sit)PaO2) in 19 out of 22 controls and in all but one cirrhotics. The magnitude of this postural change was significantly (p = 0.04) greater in cirrhotics (9.6 ± 5.3%) compared to controls (6.7 ± 3.7%). In the subset of cirrhotics younger than 60 yrs and with PaO2 greater than 80 mmHg in sitting position, the Δ(sup-sit)PaO2 in recumbency further increased to 12 ± 5.8%, significantly (p = 0.014) greater than in same subgroup of controls (7.1 ± 3.8%)., Conclusions: In mild/moderate liver cirrhosis the postural variations in PaO2 follow the normal trends, but are of greater magnitude probably as a consequence of hypoventilated units of lung for postural and disease-linked tidal airway closure, resulting in more pronounced recumbent hypoxemia ("clinodeoxia")., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Expiratory CT scan is usually obtained as supplement to normal inspiratory CT scan to recognize air-trapping, which is expression of small airways obstruction. In some patients the air-trapping may be the only sign of an early-stage small airways disease in an otherwise normal lung.The purpose of this article is to illustrate pathologic conditions, namely obliterative bronchiolitis, in which expiratory CT scan can be abnormal despite normal inspiratory CT examination, and to highlight indications for this technique in patients with clinical and functional suspect of bronchiolar obstruction.

Aim: The prevalence of respiratory diseases has been assessed in community based epidemiological studies. General practice is the ideal position to intercept chronic respiratory illness and manage the first level of follow up as well. Aim of this study was to obtain General Practitioners (GPs) data about management and clinical setting of patients with respiratory diseases., Methods: This is a prospective observational study; 272 Italian GPs were involved and equally distributed on the Italian territory. The interviews were performed by means of a questionnaire consisting in which consisted of 25 questions regarding individual demographics, catchment area, professional behavior, health attitudes., Results: Each GP reported that about 13% of the pooled patients had a respiratory disease. Concerning as for chronic respiratory illnesses, spirometry was frequently prescribed and in these patients 63% of the interviewed GPs thought that the lung functional test was fundamental. GPs also reported the importance of improving health education, well aware of its importance in the prevention of respiratory diseases; and furthermore in improving the current health system organization. As for with regard to cigarette smoke, interviewed GPs reported that the 26% of their assisted subjects were smokers and the commitment to discouraging the smoking habit was very high., Conclusion: This is a large National survey that involved GPs and real life data about management of patients with respiratory diseases. The role of GPs in the management of chronic respiratory patients represents an important tool valuable in increasing primary care identification, education and treatment of respiratory diseases.

Introduction: The strategies patients use to manage their asthma (coping) have been found to be associated with clinical and patient-reported outcomes., Objectives: The aim of this large cross-sectional survey is to assess the use of coping methods employed by patients with asthma and to explore the ability of general practitioners (GPs) to correctly identify these strategies., Methods: A modified Coping Orientations to Problem Experienced Questionnaire was completed by patients with asthma and their physicians., Results: The survey was completed by 3089 GPs (69% male; mean age 55 ± 6) and by 6264 patients (52% male; mean age 45 + 14). Active strategies were reported as the predominant method of coping by 51-59% of patients, whilst passive/avoidant techniques accounted for 12-28%. GPs believed the active coping methods were employed primarily by 35-45% of patients and the passive/avoidant methods by 8-26%. Physicians were able to identify the specific strategy used by a patient in 34%-64% of cases. The ability to identify the use of active strategies rather than the passive/avoidant was significantly higher (T test 8,250, p < 0.0001). Coefficient of concordance between GPs' and patients' answers was fair., Conclusions: These results revealed the extent of maladaptive coping strategies used by patients and the tendency for physicians to underestimate these. These observations may well represent two obstacles in improving asthma clinical outcomes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Many respiratory diseases are chronic conditions that are strongly linked with the patient-physician relationship, disease perception and therapy adherence. The aim of the present study was to evaluate patient's viewpoint about the different aspects involved in their respiratory diseases., Methods: This is a prospective observational survey. 46 Italian medical centres were involved and equally distributed. The interviews were carried out and were performed by means of a questionnaire which consisted of 32 questions regarding lung disease, modality of access to medical facilities, therapy and level of medical assistance., Results: 1116 patients were enrolled and the most important respiratory symptoms referred were: dyspnoea (69%), chronic phlegm (28%), cough (13%). During programmed visits 98.3% and 98.8% of interviewed patients knew were aware of asthma and COPD respectively, percentage that dropped, during emergency accesses, to 1.7% and 1.1% knew to have asthma and COPD respectively. Primarily were prescribed 1.67 spirometry/patient/year while only the 2% of patients referred to have performed a blood gas analysis. The 18% of patients spontaneously discontinued the therapy, considering it too complex. The average time that patients identified as being used by the doctor to perform the visit was of 22 minutes, with an high mean medical assistance satisfaction score., Discussion: There has been little research examining what factors may influence patient acceptance and participation of chronic respiratory diseases. Our national survey demonstrated that a good patient-physician relationship represents one of the first points in the successful management of respiratory diseases., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To estimate the prevalence of partly controlled and uncontrolled asthmatic patients, to evaluate quality of life and healthcare resource consumption., Methods: Cross-sectional phase followed by a 12-month prospective phase. Asthma Control Test and the EQ-5D were used., Results: 2853 adult patients recruited in 56 Hospital Respiratory Units in Italy were evaluated: 64.4% had controlled asthma, 15.8% partly controlled asthma and 19.8% were uncontrolled. The mean (SD) EQ-5D score was 0.86 (0.17) in controlled, 0.75 (0.20) in partly controlled and 0.69 (0.23) in uncontrolled patients (p<0.001 between groups). The number of patients requiring hospitalization or emergency room visits was lower in controlled (1.8% and 1.6%, respectively) than in partly controlled (5.1% and 11.5%) and uncontrolled (6.4% and 18.6%). A combination of an inhaled corticosteroid and a long-acting beta-2 agonist was the reported therapy by 56.0% of patients, with the rate of controlled asthma and improved quality of life being higher in patients on extrafine beclomethasone/formoterol compared to budesonide/formoterol (p<0.05) and fluticasone/salmeterol (p<0.05 for quality of life)., Conclusions: Asthma control is achieved in a good proportion of Italian patients. Differences may be detected in a real-life setting in favor of extrafine beclomethasone/formoterol combination., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Patient-physician communication and patients' knowledge about asthma are relevant factors that influence health outcomes. The aim of this study was to explore general practitioners' (GPs) behaviors, asthma patients' knowledge requirements, and the relationship between physicians' communicative issues, and failures in patients' knowledge., Methods: GPs participating in a continuing medical education program on asthma completed an ad hoc survey on communicative style and recruited at least three adult asthma patients to indicate, among 10 options, three aspects of asthma about which they felt less informed., Results: The survey was completed by 2332 GPs (mean age 54.39 ± 5.93 years) and 7884 patients (mean age 49.59 ± 18.03 years). Several ineffective strategies emerged in the physicians' behaviors: 28.5% of GPs did not encourage patients to express doubts, expectations, or concerns; 39.4% tried to frighten patients concerning disease-related risks; only 25.7% used a written action plan. In addition, 18.6% of GPs were not averse to informing the patient about potential side effects; 16.3% did not try to simplify asthma treatment; approximately 30% considered ease of use when selecting drugs; 18% were not disposed to carry out a partnership with the patient; 36.9% were unlikely to involve the patient in asthma management; and 73% tried to retain control over their patients. Finally, 90.3% of GPs declared they want to be consulted before any treatment change. The three topics on which patients felt less informed were the meaning of asthma control (14% of patients); integration of asthma into daily life (13.3%); and periodic checkups (12.7%). There were significant associations between patients' choices and physicians' answers., Conclusion: These results demonstrate that in general medicine the recommendations of international guidelines on education, communication, and development of a doctor-patient partnership are still ignored and that patients' educational priorities may differ from those identified by medical specialists and by patients belonging to patients' associations.

Background: We investigated the correlation between patients' characteristics, including anxiety and depression, and the level of asthma control evaluated by asthma control test (ACT), a self-administered validated questionnaire., Methods: This is a cross-sectional study on asthmatic outpatients of three Italian hospitals. Demographic data, spirometry, anxiety and depression scores as well as the level of asthma control from 315 patients were collected., Results: Patients with poorly controlled asthma were more frequently women, older, with a worse pulmonary function, obese, more anxious and/or more depressed. Four different independent factors associated with poor asthma control evaluated by ACT have been found: FEV(1)<60% (odds ratio, OR: 6.52), anxiety (OR: 3.76), age > or =65 years (OR: 2.69), and depression (OR: 2.45). The presence of anxiety and depression was associated with a higher healthcare utilization. Finally, we found a high level of agreement between ACT and multidimensional GINA approach in evaluating asthma control, with a concordance in 239 patients (81% of the population)., Conclusion: There is a close correlation between anxiety and depression, and a poor asthma. A better understanding of this association may have major clinical implications, mainly in patients with poor controlled asthma in whom the presence of anxiety and depression should be investigated., (Copyright 2009 Elsevier Ltd. All rights reserved.)

It has been documented that tiotropium is less likely to induce oxygen desaturation in stable COPD patients compared to long-acting beta2-agonists (LABAs) and combined administration of a LABA and an inhaled corticosteroid (ICS) reduces the potential for acute effects of LABA on blood-gas tensions. In this study, we have compared the acute effects of tiotropium 18 microg and salmeterol/fluticasone combination (SFC) 50/250 microg on arterial blood gases in 20 patients with stable COPD. Each subject was studied on 2 days, separated from one another by at least 4 days. Blood specimens were taken just before the inhalation and at 15, 30, 60, 180 and 360 min after inhalation of each treatment, and spirometry was performed at the same time points. As expected, both treatments significantly improved FEV1 (greatest changes were 0.20 L, 95% CI: 0.13-0.27 at 360 min after tiotropium; and 0.13 L, 95% CI: 0.06-0.19 at 180 min after SFC). The greatest mean changes from baseline in PaO2 were -1.7 (95% CI: -4.0 to 0.6)mmHg, p=0.134, after tiotropium; -0.8 (95% CI: -2.2 to 0.6)mmHg, after SFC. Both changes were observed after 15 min. Both drugs caused a small decrease in PaCO2 (greater changes: -1.9 (95% CI -3.2 to -0.6)mmHg, p=0.005 at 60 min after tiotropium; and -2.4 (95% CI: -3.5 to -1.3) mmHg, p=0.0002 at 180 min after SFC). These results indicate that both tiotropium and SFC are able to induce a significant long-last bronchodilation without affecting arterial blood gases. Moreover, they confirm that the impact of tiotropium on PaO2 is small and without clinical significance and the addition of a LABA to an ICS can reduce the potentially dangerous acute effect of the LABA on blood gases.

Background: It has been suggested that the antihypertensive agent nebivolol, a beta1-adrenoceptor-blocking agent that modulates the endogenous production of nitric oxide, is preferable to 'conventional' beta1-blockers in hypertensive patients with airway dysfunction., Objectives: Since beta1-blockade by nebivolol is larger after repeated dosing than after a single oral intake, we have explored its effect on pulmonary function after a 2-week treatment in hypertensive patients with mild to moderate COPD., Methods: A single-blind crossover design was used. Twenty patients with COPD as selected above and with a diastolic blood pressure of 95-110 mm Hg after 1 week of placebo run-in were entered into the two 2-week active treatment periods with either 5 mg nebivolol (n = 10) or 30 mg nifedipine gastrointestinal-transport-system (GITS) (n = 10) taken for a period of 2 weeks. After a further 1-week washout, subjects were crossed-over to receive the other drug for 2 additional weeks. At each visit, changes in spirometric indexes and the interaction with the bronchodilator effect of salbutamol were investigated. Moreover, systolic and diastolic blood pressure (BP) together with heart rate were manually measured in order to evaluate the cardiovascular effects of the different treatments. Throughout the study, patients recorded symptoms., Results: Similar and significant reductions in systolic and diastolic BP were observed with both treatments. The impact of nifedipine on FEV1 was not significant (p > 0.05), while that of nebivolol was slight. The maximum response to salbutamol was slightly decreased with either nebivolol or nifedipine GITS. Day-to-day airway obstruction control, interpreted from patient recordings of symptom scores and inhaler use, was similar with both treatments., Conclusions: Our pilot study suggests that the use of nebivolol in hypertensive patients with stable mild to moderate COPD was safe during a 2-week trial. Evaluation of longer time periods, larger patient numbers with more severe COPD or during exacerbations is warranted., (Copyright 2004 S. Karger AG, Basel)

Background and Aim of the Work: The follow-up of sarcoidosis is usually performed by invasive tools such as thoracic biopsy, supported by Broncho-Alveolar Lavage (BAL), Gallium-scintigraphy and Gadolinium Magnetic Resonance Imaging (Gd-MRI) to evaluate the degree of disease. Its pathogenesis can be ascribed to an accumulation of cells due to the disregulation of the immune system which involves Th1/Th2 cells as well as the soluble factors they generate. We evaluated serum cytokine and membrane marker levels (cytokine network) in sarcoid patients in order to study the correlation with the disease activity, in particular with the occurrence of sarcoidosis relapses., Patients and Methods: Seven sarcoid patients clinically stable without therapy, at different stages, were enrolled in our study. Cytokine and membrane marker serum values were measured monthly for 24 months, after a six-month period of run-in, by ELISA assay and MoAb indirect immunofluorescence, respectively., Results: In some patients at the first and second stages of the disease we observed MCP-1 and inflammatory cytokine peaks and, moreover, MCP-1 values were increased before other cytokine values. After three subsequent increases of these parameters were observed, according to our personal experience, Gadolinium-MRI confirmed the presence of an increase of the lesion and therefore our hypothesis of sarcoidosis relapse. Only one patient at stage III showed constantly elevated values of fibro-angiogenic cytokines and membrane receptors of the TNF receptor family., Conclusions: Cytokine network monitoring could be a non-invasive means of following up the clinical course of sarcoidosis.

The usefulness of a metered-dose inhaler equipped with a new spacer device (Jet spacer) was evaluated and compared with that of a standard actuator in the administration of high-dose inhaled beclomethasone dipropionate (0.5 mg four times daily) to adults with moderate asthma. After a 2-week run-in period, 36 patients were enrolled in a 4-week study according to a randomized, parallel-group design. Efficacy was assessed by measurements of pulmonary function and daily beta 2-agonist consumption. Morning serum and 24-hour urinary cortisol levels were measured at baseline and after treatment; adrenocorticotropic hormone (ACTH) stress testing was also done. Spirometric parameters significantly improved in both groups; peak expiratory flow rate measured at the final visit was significantly higher (P < .01) in the group using the Jet spacer than in patients using the standard actuator. Beta 2-agonist consumption decreased in both groups. The number of patients with a normal response to ACTH was significantly higher (P < .01) in the Jet group than in the standard actuator group; concomitant urinary cortisol excretion decreased significantly (P < .05) in the standard actuator group. Local irritation was reported by 1 patient in the Jet group and by 2 patients in the standard actuator group. Use of the new Jet spacer was found to reduce the potential for adrenal suppression and increase the efficacy of high-dose inhaled beclomethasone dipropionate given to adults with asthma.

In eight asthmatic subjects a randomized, double-blind, placebo controlled study was performed to investigate the effect of inhaled ketanserin, a 5-HT2 receptor blocking agent, in a dose of 10 mg given 30 min before test, on adenosine-induced bronchospasm. The protective effect of ketanserin was significant in all patients, even though it altered basal bronchomotor tone in only two subjects. On the contrary, ketanserin did not inhibit histamine-induced bronchoconstriction in four of these eight asthmatics, even though it modified sensitivity and reactivity in one of them. The results suggest that ketanserin influence on adenosine bronchial reactivity and sensitivity was not due to the bronchodilator effect of ketanserin itself or to its antihistaminic activity. We have no certain explanation for the inhibition of adenosine-induced bronchoconstriction elicited by ketanserin. It is possible that 5-HT may play, at least in part, a role as mediator of adenosine-induced bronchoconstriction.

The effect of sulbactam/ampicillin (500 mg/1000 mg) every 12 hours taken for seven days on the steady-state pharmacokinetics of theophylline was studied among 12 patients suffering from chronic obstructive pulmonary disease. Theophylline concentrations were measured serially for 12 h by the method of polarized immunofluorescence (Abbott TDx system). No influence of sulbactam/ampicillin was detectable on the theophylline half-life, clearance or volume of distribution. It was concluded that both drugs could be administered concomitantly without any dosage adjustment of theophylline.

Sixty adult patients, 31 men and 29 women, aged 44 to 60, and affected by acute bronchitis of probable bacterial aetiology were randomly divided into 3 groups of 20 and treated respectively with: 1) morniflumate (one 700 mg tablet twice a day) + amoxicillin (one 1 g tablet twice a day); 2) feprazone (one 200 mg tablet twice a day) + amoxicillin (one 1 g tablet twice a day); 3) amoxicillin (one 1 g tablet twice a day). Mean therapy duration was 9 days. The action of the drugs under study was assessed by objective chest examination and by evaluating the modifications of cough intensity and frequency, chest pain expectorating difficulty, amount of expectoration, body temperature. The overall assessments were completed by side-effect recording and by laboratory examinations carried out at the beginning and end of the study. Checks were made regularly on admission, and in the 3rd, 5th, 7th and last day of therapy. The above mentioned parameters showed a quicker regression of bronchial inflammation in the subjects treated also with the antiinflammatory drug compared to those treated only with the antibiotic. Furthermore, in the subjects treated with morniflumate such improvement was more rapidly achieved compared to those who received feprazone. The analgesic and antipyretic effects of morniflumate were also remarkable. All tested drugs were well tolerated.

Ciprofloxacin was given orally in dosages of 250 mg or 500 mg every 12 hours for a period of 8-13 days. Most patients had chronic bronchitis in the acute stage. The favourable results achieved and the complete absence of side effects show that ciprofloxacin is a useful drug in the treatment of respiratory tract infections.

Patients who were cigarette smokers suffering exacerbations of chronic bronchitis were examined in eight outpatient clinics in five regions of Italy, three from the South (Campania, 82 patients; Sicily, 82 patients; and Puglia, 29 patients) and two from North (Lombardy, 33 patients; and Liguria, 50 patients). Haemophilus influenzae was the most frequently isolated bacterium in the patients' sputum (in 30% of the total group), followed by Streptococcus pneumoniae (in 20%), Staphylococcus aureus (in 25%), and Branhamella catarrhalis (in 7%). H. influenzae was the most common bacterium in the South (in 37%) and S aureus in the North (in 13%). Smoking index scores (number of cigarettes smoked daily x years of smoking) were 827 in patients in whom H influenzae was isolated; 691 in patients with S aureus; 599 in patients with S pneumoniae; 542 in patients with B catarrhalis; and 446 in patients in whom no isolates were found. Pulmonary function was most severely decreased in patients positive for H influenzae and S aureus. The results indicate an association between heavy cigarette smoking and lower respiratory tract infections that is influenced by regional differences.

The present study was undertaken in order to investigate the penetration of cefonicid, a long-acting parenteral cephalosporin, with enhanced activity against most gram-positive and gram-negative pathogens, into human lung tissue and lymph nodes in patients undergoing open thoracotomy. Samples of lung tissue, lymph nodes and serum were obtained at various times after a single intramuscular dose of 1 g. The concentration of cefonicid was assayed by an agar diffusion method with Bacillus subtilis used as the test organism. The mean concentrations of cefonicid in serum at 2, 4, 8, 12 and 24 h after the injection were 91.5, 66.1, 35.7, 21.8 and 2.9 micrograms/ml, respectively. The mean levels of cefonicid into the hilar lymph nodes at the same times were 22.3, 18.7, 12.0, 6.9 and 1.5 micrograms/ml, respectively, while its concentrations in lung tissue were lower than those in lung lymph nodes up to the 12th hour (12.1, 14.6, 7.8, 5.4 and 1.9 micrograms/ml, respectively). Our results show that cefonicid was well distributed in interstitial fluid from which pulmonary lymph is formed and that its concentrations in lung tissue and lymph nodes were sufficient to inhibit most pathogens involved in respiratory tract infections. This finding was considered important, because it demonstrated that the high binding by plasma protein of cefonicid did not prevent it from entering lung tissue and fluids in useful quantities.

The trial population consisted of 50 patients suffering from acute exacerbations of chronic bronchial disease processes. Forty patients were treated with an extempore combination of cefuroxime and N-acetylcysteine at the doses of 2 g and 600 mg/day respectively in two i.m. administrations. The other 10 patients were treated with N-acetylcysteine alone at the same dose. Respiratory tract clinical and instrumental parameters were investigated, and bacteriological tests were performed on sputum samples before and after treatment. Tolerance of the treatment was assessed on the basis of measurement of blood-chemistry parameters.

Bronchial provocation tests (TBP) allow to detect airways hyperreactivity in asthmatics. Twenty asthmatic children and sixteen rhinitics underwent a standard methacholine challenge and a free running exercise test on two separate days. Metacholine challenge pointed out bronchial hyperreactivity in 90% of the asthmatics. An exercise induced bronchospasm occurred in 70% of them. TPB resulted positive also in 18% of the rhinitics. Our study confirms diagnostic usefulness of the TBP and a good correlation between both tests.

Twenty patients (10 males and 10 females), ranging in age from 53 to 81 years, were treated with ceftazidime, 2-3 g/day i.m., for 12 to 15 days. All patients were suffering from moderate to severe infections of the lower respiratory tract (6 cases of pneumonia and 14 cases of acute exacerbation of chronic bronchitis). In addition, almost all patients presented severe local and general predisposing factors (three patients with lung cancer, two with bronchiectasis and 14 with respiratory insufficiency). The aetiological agents responsible for the infections were mainly Gram-negative bacteria (6 Klebsiella pneumoniae, 4 Haemophilus influenzae, 4 Pseudomonas aeruginosa and 3 Proteus strains). The clinical and microbiological results of the treatment were good. With the exception of one case of maculopapular rash, none of the patients complained of adverse reactions and no toxic effects were observed.