Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27%) and total cells (-42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3%), macrophages (+16.5%), and total cells (-65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.

Study of release of eosinophil cationic proteins (ECP and EPX) in the hypereosinophilic syndrome (HES) and other hypereosinophilic conditions.

BACKGROUND: Up to date, the etiology and the pathogenesis of HES are still unknown and particularly it is unclear why eosinophils in HES are more aggressive towards tissues than in other eosinophilic conditions. METHODS: We assessed the cationic proteins ECP and EPX serum concentrations, their in vitro release from polymorphonuclear cell culture, and the monoclonal antibodies EG1 and EG2 in 3 patients with HES, 6 patients with other hypereosinophilic conditions and 20 healthy control subjects. RESULTS: Serum ECP and EPX concentrations were higher in eosinophilic patients than in healthy subjects. Hypereosinophilic patients had more EG2+ cells than healthy subjects, but EG2+ rate failed to differentiate HES from other hypereosinophilic conditions (p = 0.074). Moreover, the release in vitro of ECP and EPX was significantly higher in HES patients (p < 0.05). CONCLUSIONS: Our preliminary results seem to suggest the importance of functional data, such as ECP and EPX release, in differentiating HES from other hypereosinophilic diseases. Particularly, ECP and EPX release in vitro is higher in cell cultures from HES patients than from patients with other hypereosinophilic conditions.

Haemodynamic response during initiation of non-invasive positive pressure ventilation in COPD patients with acute ventilatory failure.

The aim of this study was to check non-invasively the acute haemodynamic effects of non-invasive positive pressure ventilation (NPPV) initiation in patients with chronic obstructive pulmonary disease (COPD) and acute ventilatory failure (AVF). Nineteen consecutive COPD patients with AVF were evaluated clinically and echocardiographically during spontaneous breathing with O2 supplementation and during NPPV plus O2. NPPV was administered with a scheduled inspiratory pressure of 15 cmH2O and an expiratory pressure of 4 cmH2O, via facial mask. Arterial blood gas improved significantly (pH and PaCO2; P < 0.001) during NPPV administration in all patients; none had hypotension or acute arrhythmia. Doppler echocardiographic evaluation was feasible in most of the patients (16/18). With reference to baseline values, no significant changes in pulmonary artery pressures and cardiac output (CO) were observed by Doppler echocardiography in most patients. Only four patients (21%) showed a significant reduction (> 15%) of CO during NPPV. No correlation was found between decreased CO and baseline data, but three patients showing CO reduction had poor tolerance to mask ventilation and did not improve respiratory rate during NPPV. It was concluded that the initiation of NPPV by facial mask does not alter haemodynamics acutely in most COPD patients with AVF, but individual patients may experience reduction in CO in spite of adequate oxygen saturation levels. This suggests that caution should be used when applying pre-determined and fixed pressures during NPPV. Monitoring haemodynamics by Doppler echocardiography may be useful for early detection of haemodynamic alterations due to NPPV application in patients with AVF.

[Pulmonary complications in diabetes mellitus]. / Complicanze polmonari in corso di diabete mellito.

The lung is not considered a target organ in diabetes mellitus. In English language literature there are many papers showing the opposite. Many studies demonstrated a thickened alveolar epithelial and pulmonary capillary basal lamina and a reduced lung elasticity, others showed that these histopathological alterations developed into functional abnormalities: reduced lung volumes, reduced pulmonary diffusion capacity and elastic recoil. The pathogenesis is currently thought to involve the nonenzymatic glycosylation (NEG) of tissue proteins inducing an alteration in connective tissue. In patients with diabetic autonomic neuropathy there is an abnormal basal airway tone due to an alteration in vagal pathways: these patients have a reduced bronchial reactivity and bronchodilatation. Diabetic patients have an increased propensity to acquire infections, in particular tuberculosis and pulmonary fungal diseases (coccidioidomycosis, aspergillosis and mucormycosis). The frequency of occurrence of tuberculosis is reported to be four times than in non diabetics, there is a predilection for the lower lobes and the disease is more aggressive in poorly controlled diabetes mellitus. Pulmonary mucormycosis is an infection caused by Phycomycetes, the fungus has the propensity to invade vascular structures giving hemoptysis and leading to a high mortality unless diagnosed promptly. The mechanism for the increased susceptibility to infection is due to an alteration in chemotactic, phagocytic and bactericidal activity of polymorphonuclear leukocytes.

Histoplasmosis capsulati in Italy: autochthonous or imported?

Reports of a few apparently autochthonous cases of human histoplasmosis and results of epidemiological research suggested the autochthonous presence of the disease in Italy. Identifying two new histologically documented cases of Italian patients, who had never been abroad, and, the positive results of a histoplasmin reactivity survey carried out in the Province of Cremona, Italy confirmed this possibility.

Severe exacerbations of chronic obstructive pulmonary disease treated with BiPAP by nasal mask.

Bi-level pressure support ventilation via a nasal mask (NIPSV) was provided to 28 consecutive unselected patients with acute respiratory failure due to exacerbation of chronic obstructive pulmonary failure (COPD). If NIPSV improved gas exchange within 2 h, it was continued. Otherwise, patients would be promptly intubated. The patients median age was 68 years (minimum 56, maximum 82). The arterial blood gas drawn before initiating NIPSV showed (FiO2 21%) a mean PaO2 of 41.3 +/- 6 mm Hg, a mean PaCO2 of 66 +/- 15 mm Hg and a mean pH of 7.31. Upon admission the mean respiratory rate was 36 breaths/min and the median Apache II score was 20.5 (minimum 13, maximum 32). Despite oxygen administration all patients failed to improve their PaO2 and/or showed a consistent and dangerous hypercapnic response. NIPSV was performed with a median inspiratory positive airway pressure of 14 cm H2O (minimum 10, maximum 20) and a median expiratory positive airway pressure of 4 cm H2O (minimum 3, maximum 6). Eighteen patients (64%) were successfully ventilated with NIPSV, while in 10 (36%) NIPSV failed. A high Apache II score, but not admission blood gas exchange or respiratory rate, seems to be correlated with the failure to ventilate with NIPSV. The results of our preliminary experience suggest the use of NIPSV as an initial approach to acute respiratory failure due to exacerbation of COPD, particularly in patients with an Apache II score of less than 29.

[Severe bronchial spasm crises induced by topical administration of eyedrops with timolol base, a non-selective beta blocking agent]. / Gravi crisi broncospastiche indotte da applicazione topica di gocce oculari a base di timololo, un beta bloccante non selettivo.

Since their introduction in clinical practice beta-blocker drugs are known to be able to induce bronchospasm. However, this adverse effect may develop only in subjects with asthma, chronic bronchitis and/or airways hyper-reactivity. Although this potentially adverse effect of beta-blockers on the airways has long been recognized, its mechanism in inducing bronchospasm remains unclear. The Authors report a case of severe bronchoconstrictive episodes with respiratory failure following the administration of a timolol ophthalmic solution in a 51 yr old woman. Pharmacokinetics, preventive and therapeutic aspects of timolol eyedrop-induced bronchospasm are discussed.