Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters.

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Sleep quality and associated daytime consequences in patients with idiopathic pulmonary fibrosis.

OBJECTIVE: The aim of this study was to describe sleep quality and associated daytime consequences in idiopathic pulmonary fibrosis (IPF). SUBJECTS AND METHODS: Fifteen patients with IPF and 15 control subjects matched on age and anthropometric variables were included in the study. Sleep quality and its daytime consequences were assessed by clinical interview, the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes in Sleep Questionnaire (FOSQ), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale and attended all-night polysomnography. RESULTS: Polysomnography revealed a decrease in sleep efficiency and slow wave sleep, and an increase in stage 1 sleep and arousal index in IPF patients compared to controls. Daytime tachypnea persisted during sleep. Oxygen saturation below 90% was observed during 34.3 +/- 37.3% of the total sleep time (TST). Quality of sleep and daytime function were moderately to significantly impaired based on the PSQI and FOSQ. The total FOSQ score was negatively correlated with TST with oxygen saturation below 90% (p = 0.01, r = -0.62). FSS scores were correlated with TST at oxygen saturation below 90% and mean oxygen saturation during sleep (p = 0.002, r = 0.74, and p = 0.007, r = -0.66, respectively). CONCLUSIONS: Our data suggest significant sleep disruption and consequent impairment of physical and social functioning in patients with IPF. In the absence of effective treatments for IPF, the improvement of sleep quality should be a primary therapeutic goal.

Apoptosis in lung injury and fibrosis.

Pulmonary fibrosis is characterised by fibroblast accumulation and alveolar epithelium denudation. Increased apoptosis of alveolar epithelial cells and decreased apoptosis of fibroblasts may play an important role in the pathogenesis of disease. Inflammatory cells can modulate apoptosis of other cell types, both by removal of apoptotic debris and by cytokine production, thus preserving a pro-fibrotic environment. In the present review, some of the mechanisms by which apoptosis may contribute to the pathogenesis of idiopathic pulmonary fibrosis are described.

Expression of bcl-2 protein in bronchoalveolar lavage cell populations from patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To investigate changes in the expression of the antiapoptotic protein bcl-2 in bronchoalveolar lavage fluid (BALF) cell populations in patients with idiopathic pulmonary fibrosis (IPF). STUDY DESIGN: Ten patients with IPF underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in the area of maximal radiographic shadowing (based on high-resolution computed tomography findings). Results were compared with those of 10 normal people in the control group. Cellular bcl-2 expression was identified using an immunoperoxidase staining method. RESULTS: A statistically significant (P < .001) increase in the expression of bcl-2 in BALF neutrophils and eosinophils was observed in patients with IPF as compared with controls. BAL macrophages exhibited only a slight (statistically insignificant) increase in bcl-2 expression in IPF patients. No bcl-2 expression was observed in BAL lymphocytes from IPF patients in contrast to the control group. CONCLUSION: The overexpression of bcl-2 on BALF neutrophils and eosinophils, cells that characterize the special cellular profile of alveolitis in IPF, could be one of the pathophysiologic mechanisms of this disease.

Detection of sarcoidosis associated fasciitis by uptake on a FDG PET scan: a novel finding.

We report a case of a sarcoidosis patient with bilateral calf and thigh stiffness who was noted to ha ve intense linear FDG uptake on a PET scan that localized to the fascia of his calves and theighs. His serum creatine kinase level was normal. Fasciitis has rarely been reported to be detected on FDG PET scans, and, to our knowledge, never in a sarcoidosis patient. FDG PET may have a role in identifying fasciitis or myositis when a patient has muscular complaints and no clinical or laboratory evidence of muscle injury.

Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study.

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Epidemiology of interstitial lung diseases in Greece.

INTRODUCTION: Few data are available on the epidemiology of interstitial lung diseases (ILDs), especially after the current classification of idiopathic interstitial pneumonias. The aim of this study is to provide data on the epidemiology of ILDs in Greece, under the ATS/ERS international consensus. METHODS: Departments of Pneumonology were contacted and asked to complete a questionnaire for every case of ILD that was alive on 2004 as well as for every new case from 1st January 2004 to 31st December 2004. Questions on the patients' demographic data, the exact diagnosis and the procedures used to establish the diagnosis were included. Centers covering about 60% of the Greek population have been analyzed. RESULTS: A total of 967 cases have been registered. The estimated prevalence of ILDs is 17.3 cases per 100,000 inhabitants. The estimated annual incidence of ILDs is 4.63 new cases per 100,000 inhabitants. The most frequent disease is sarcoidosis (34.1%), followed in decreasing order by idiopathic pulmonary fibrosis (19.5%), ILD associated with collagen vascular diseases (12.4%), cryptogenic organizing pneumonia (5.3%), histiocytosis (3.8%), and hypersensitivity pneumonitis (2.6%). Unclassified ILD or not otherwise specified accounted for the 8.5% of prevalent cases. CONCLUSIONS: These data suggest that sarcoidosis and idiopathic pulmonary fibrosis are the most frequent ILDs in our population. In comparison with the few previous reports, interesting dissimilarities have been observed.

Health-related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary disease (overlap syndrome).

The association of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD) is not rare as COPD and OSA are both frequent diseases. The aim of this study was to determine the effect of OSA on quality of life (QOL) in patients with overlap syndrome (OVS). Thirty subjects with OVS and 15 control subjects participated. The St George's Respiratory Questionnaire (SGRQ) was used to determine QOL. The control group included subjects with COPD and no evidence of OSA by overnight polysomnography. All subjects were habitual snorers with normal Epworth Sleepiness Scale scores. Significant differences were found between the groups for the total score and each of the three components of the SGRQ suggesting worse QOL in OVS patients (symptoms 54.9 +/- 18.9 vs. 38.2 +/- 19.3, p = 0.008; activity 59.2 +/- 16.2 vs. 44.4 +/- 11.3, p = 0.003; impacts 35.2 +/- 23 vs. 20.8 +/- 8.7, p = 0.025 and total 45.7 +/- 17.7 vs. 30.9 +/- 8.7, p = 0.004 in OVS patients and control group, respectively). Obstructive sleep apnoea has a major impact on QOL in patients with OVS and can exist in COPD patients with habitual snoring even in the absence of daytime sleepiness. Further studies are needed to determine the impact of OSA treatment on QOL and morbidity in this population.

Overexpression of bcl-2 protein in bronchoalveolar lavage lymphocytes and macrophages in sarcoidosis.

BACKGROUND AND OBJECTIVES: Apoptosis, also known as programmed cell death, probably correlates with the pathophysiologic mechanisms of alveolitis in sarcoidosis. Our purpose was to investigate any changes in the expression of the antiapoptotic protein Bcl-2, one of the most important inhibiting factors of apoptosis, in bronchoalveolar lavage fluid (BALF) cell populations in patients with sarcoidosis. SUBJECTS AND METHODS: Fiberoptic bronchoscopy with BAL was performed in 13 patients with active sarcoidosis (10 patients with stage I and 3 with stage II disease based on chest radiography). None of them was under treatment with corticosteroids. Cellular Bcl-2 expression was identified using an immunoperoxidase staining method. Ten normal subjects served as control group. RESULTS: BALF lymphocytes and macrophages in sarcoid patients exhibited a significant increase in the expression of Bcl-2 compared with the control group (p < 0.001). A Bcl-2 expression of 80.7 +/- 8.5% in the lymphocytes and 77.4 +/- 8.9% in the macrophages was observed in sarcoidosis versus 32.2 +/- 13.8% and 19.6% +/- 7.6% in normal subjects, respectively. The percentages of Bcl-2 expression in the lymphocytes were positively correlated with BALF CD4/CD8 ratio values (p = 0.02, r = 0.63). CONCLUSIONS: Our results suggest that the antiapoptotic protein Bcl-2 is overexpressed in alveolar lymphocytes and macrophages, which characterize the alveolitis in sarcoidosis and could provide insights into the pathogenesis of the disease and prove useful as a marker of disease activity or response to therapy.

Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.

BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.

Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-gamma) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-gamma-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-gamma 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-gamma-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.

Acute interstitial pneumonia.

The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.

Theophylline induces a reduction in circulating interleukin-4 and interleukin-5 in atopic asthmatics.

Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that theophylline may also have anti-inflammatory or immunomodulatory effects in asthma. This study investigated whether theophylline administration has an impact on serum levels of interleukin (IL)-4 and IL-5 in asthmatic patients. Eight asymptomatic patients aged 30+/-1.5 yrs (mean +/- SEM) with mild atopic asthma were given a single daily dose of theophylline 150 mg or placebo in an on (theophylline)-off (placebo)-on (theophylline)-off (placebo) protocol with a 3-week duration of each on- or off- interval. Determination of serum IL-4 and IL-5 was done at baseline for all subjects and on the last day of each 3-week interval for the patients under study. Serum IL-4 levels were: 35+/-6 (baseline), 19+/-3 (on-1 interval), 29.5+/-4 (off-2), 15+/-2 (on-3) and 26+/-4 pg x mL(-1) (off-4), while IL-5 levels were 27+/-5, 18+/-4, 28+/-5, 17+/-4 and 28+/-5 pg x mL(-1), respectively. Spirometry was unchanged during the study and serum theophylline levels at the end of the two on-periods were 4.5+/-0.05 and 4.2+/-0.07 microg x mL(-1), while all patients remained asymptomatic. In conclusion, the administration of a low, single, daily dose of oral theophylline in asymptomatic patients with mild atopic asthma seems to reduce circulating interleukin-4 and interleukin-5.

A comparison of oral cefuroxime axetil and oral amoxycillin in lower respiratory tract infections.

We assessed oral cefuroxime axetil in an open study of 30 patients with lower respiratory tract infection and then compared oral cefuroxime with oral amoxycillin in a randomized double blind study in a further 40 patients. Satisfactory clinical responses were obtained in 73% of patients receiving cefuroxime axetil 500 mg tid in the open study, and in the comparative study in 71% of patients receiving cefuroxime axetil 500 mg bd, in 60% of patients receiving cefuroxime axetil 500 mg tid and in 63% of patients receiving amoxycillin 500 mg tid. There were no significant differences in response rates between the three regimens in the comparative study. There were no important adverse effects in any of the patients. Oral cefuroxime axetil is safe and effective in the therapy of lower respiratory tract infections.

Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma.

A total of 132 adult asthmatics who were symptomatic on 500 microg x day(-1) inhaled beclomethasone dipropionate (BDP) were studied in an open-label randomized, parallel group, 12 week, clinical trial. The addition of 12 microg formoterol fumarate solution aerosol (pressurized metered dose inhaler) b.i.d. to BDP at a dose of 500 microg x day(-1) was compared with a higher dose of 1,000 microg x day(-1) BDP. Mean morning premedication peak expiratory flow rate (PEF) during the final week of treatment (primary end-point) increased in both groups compared to baseline. The estimated treatment difference of 20.4 L x min(-1) (95% confidence interval 3.2-37.6) after 12 weeks of treatment was statistically significant (p<0.05) in favour of the formoterol/BDP group. The overall mean morning premedication PEF for the entire treatment period was higher in the formotero/BDP group (p=0.002). The overall number of puffs of rescue medication and asthma symptom scores were less in the formotero/BDP group (p<0.01). Safety and tolerability evaluations were satisfactory in both groups. In conclusion, the results suggest that the addition of formoterol fumarate to the existing dose of an inhaled corticosteroid should be considered as an alternative to increasing the dose of inhaled corticosteroid in the inadequately controlled asthmatic.