Gabriella Pagliari

Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease

PURPOSE To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearmans rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.

Electrocardiographic Signs of Chronic Cor Pulmonale: A Negative Prognostic Finding in Chronic Obstructive Pulmonary Disease

BACKGROUND Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. METHODS AND RESULTS Two hundred sixty-three patients (217 men) with COPD, mean age 67+/-9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or >/=1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3. 45 years, respectively; Mantel-Cox test, 9.58; P=0.002). The Cox regression analysis identified S1S2S3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (PAO2-PaO2) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S1S2S3 pattern and RAO (n=14) and of patients having either S1S2S3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively (P=0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their PAO2-PaO2 during oxygen therapy was or was not >48 mm Hg. CONCLUSIONS Some ECG signs of CCP and PAO2-PaO2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.

Cognitive Impairment in chronic obstructive pulmonary disease: a neuropsychological and spect study

Abstract. Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimers disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p ≤ 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.

Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis

BackgroundA progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients.Methods100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6–12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices.Results90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54–64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40–34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure ≥ 40 mmHg was found in 6 (37.5%) patients with alveolitis.ConclusionWe found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL would be necessary to detect any infections of the lower respiratory tract that may cause further deterioration in lung function.

The Role of Bronchoalveolar Lavage in the Microbiological Diagnosis of Pneumonia in Patients with Haematological Malignancies

In the aetiological diagnosis of pulmonary infections in patients affected by haematological malignancies we evaluated the utility of bronchoalveolar lavage (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our series, we identified the agent of pneumonia in 53.5% of episodes with the best results in aspergillosis, very common in these patients. The previous empirical anti-infective treatment was modified in 14 episodes (11%). The procedure was generally well tolerated and only one patient bled. We maintain that BAL is a useful diagnostic tool for detecting the agents of pulmonary infections in patients with haematological malignancies, especially when the routine microbiological procedures fail, and it also represents a good alternative to more invasive procedures.

Bronchoalveolar lavage fluid and progression of scleroderma interstitial lung disease

Introduction:  So far no clinical or experimental evidences clearly explain how and which systemic sclerosis (SSc) patients will experience a functional and radiological progression of interstitial lung disease (ILD).

The yield of bronchoalveolar lavage in the etiological diagnosis of pneumonia in leukemia and lymphoma patients

To the Editor: Pulmonary infection is a very frequent complication in hematological malignancies. It represents the major cause of morbidity and mortality in leukemic patients. The early etiological diagnosis allows the timely start of an aimed therapy. Various invasive procedures have been proposed for this purpose: fiberoptic bronchoscope with transbronchial biopsy, transthoracic fine needle aspiration, open-lung biopsy. Yet they are associated with a high risk of complications. Bronchoalveolar lavage (BAL) performed by a fiberoptic bronchoscopy has been proposed as a good diagnostic tool for the diagnosis of pulmonary infections in immunocompromised patients (1-4). Sixty-five bronchoscopic procedures with BAL were performed in 63 leukemia and lymphoma patients. All cases presented a focal or diffuse pneumonia during the aplastic phase after an aggressive antiblastic treatment. The patients (m/f 43/20, aged 17-68) were affected by acute myeloblastic leukemia (AML) (35) , acute lymphoblastic leukemia (ALL) (6), non-Hodgkin’s lymphoma (NHL) (18), Hodgkin’s disease (HD) (4). Patients with other hematological malignancies or submitted to allogeneic bone marrow transplantation (BMT), as well as patients who had received thoracic radiotherapy, were excluded from this study. One AML patients was not evaluable because the procedure was interrupted by bleeding. The median time between the diagnosis of pulmonary infection and BAL procedure was 4 d (range 2-1 1). In all cases before the execution of BAL, routine microbiological cultural and serological tests were performed; at the onset of neutropenia a prophylaxis treatment with oral quinolonics and Amphotericin B was started. Prophylactic administration of Cotrimoxazole twice-weekly was added in ALL and LNH. At the onset of the fever all patients were treated with an empirical broad-spectrum antibiotic association according to the GIMEMA infective program (5). After 3-5 d of antibiotic therapy without improvement or recovery, antifungal therapy was added. Furthermore, in the cases with a diffuse interstitial infiltration suspect for a cytomegalovirus (CMV) infection, an antiviral treatment (Ganciclovyr) was started. In 12 patients (8 ALL and 4 LNH) therapeutic doses of Cotrimoxazole towards Pneumocystis carinii (PC) were administered, even in the absence of a specific diagnosis. The BAL fluid was stained and cultured for aerobic and anaerobic bacteria, fungi (Aspergillus and Candida species), mycobacteria, viruses (CMV, Herpes-simplex HSV, Varicella-zooster HZV, Influenza). The search for CMV was performed by immunofluorescence technique. The presence of PC in BAL was tested with optical microscopic examinations using special stains and, in the last 22 cases, with monoclonal antibodies. BAL was diagnostic in 37 cases (60 %). Fig. 1 lists the microbiological agents identified. In 13 cases pulmonary Aspergillosis was diagnosed by BAL fluid culture. In the 4 cases who performed brushing, Aspergillus isolated in BAL was present in brushing too. In 3 cases the diagnosis was confirmed by the autopsy. In 3 cases the fungus was demonstrated in a cutaneous biopsy too. In 2 patients the presence

Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P  <  0.02; healthy subjects: P  <  0.03), whereas EBC PGE2 was elevated in current (P  =  0.0065) and ex-smokers with COPD (P  =  0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P  <  0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P  <  0.01; healthy subjects: P  <  0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P  =  0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up

Backgroundβ-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters.Methodsβ-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls.ResultsThymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis.ConclusionsWe describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.

Role of ultrasound-guided transbronchial biopsy in the diagnosis of peripheral pulmonary lesions.

INTRODUCTION Endobronchial ultrasound (EBUS) can be used as an alternative to fluoroscopy to visualize a peripheral pulmonary lesion (PPL) and to provide an image guidance for transbronchial biopsy (TBB). The aim of this study was to verify the accuracy of EBUS-guided TBB in the diagnosis of PPLs. METHODS All the patients with CT-scan evidence of PPL who underwent bronchoscopy with EBUS in the period between 2008 and 2011 were retrospectively evaluated. EBUS was performed using a radial-type miniature ultrasound probe. Once obtained an EBUS image of the PPL, we measured the distance of the PPL from the outer orifice of the working channel of the bronchoscope in order to perform TBB at PPL site. RESULTS A total of 662 patients were examined. The mean diameter of lesions was 36 ± 20 mm. PPLs were visualized in 494 patients (75%) and the TBB was performed in 479 patients. Thirty-two patients were lost in follow-up and data from 447 patients were analyzed. TBB results were 255 cancers and 192 non-malignant lesions. The final diagnosis reported was 359 cases of cancer and 88 of benign lesion. EBUS-guided TBB had a sensitivity of 71% for the diagnosis of cancer, a negative predictive value of 46% and an overall diagnostic accuracy of 77%. CONCLUSIONS These data obtained from a large series of patients and using an original method show that EBUS represents a valid support to bronchoscopy and that the EBUS-guided TBB has a high diagnostic yield in the diagnosis of PPLs.