Autofluorescence bronchoscopy to identify pre-cancerous bronchial lesions.

BACKGROUND: This study aimed to assess the diagnostic yield of autofluorescence bronchoscopy (AFB) in the detection of pre-cancerous bronchial lesions in a non-selected sample of patients. METHODS: Both fiberoptic white-light bronchoscopy (WLB) and AFB using the Storz D-light system were performed on 166 consecutive patients. Biopsy specimens were taken in areas of the tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. The bronchoscopic procedures were randomly performed by two operators. RESULTS: A total of 93 patients had a positive biopsy specimen: 80 for cancer and 13 for dysplasia. AFB was abnormal or suspicious in 85 of the 93 patients with a sensitivity of 91.4%. Specificity was 50.7%. In 16 patients with normal WLB examination, AFB identified abnormal or suspicious areas which had a positive biopsy. Thus AFB significantly improved sensitivity of WLB (100% vs 82.8%, respectively, p<0.001) in the entire sample of patients studied. Data was further analysed separately for patients with dysplasia and those with cancer. Indeed, 13 of 16 patients recognized only by AFB had a histological diagnosis of dysplasia. The remaining three patients had a diagnosis of cancer (small intraepithelial neoplastic lesions). Since no other patient with dysplasia was found, AFB had a sensitivity of 100% in diagnosing dysplasia. On the other hand, excluding the 13 patients with dysplasia, WLB had a high sensitivity in diagnosing cancer (93.7%). CONCLUSIONS: The AFB Storz system showed a high sensitivity. The increase in diagnostic yield of AFB in comparison with WLB was related to the power of AFB to identify pre-cancerous bronchial lesions so showing its usefulness in the early diagnosis of lung cancer.

Effect of aqueous cigarette smoke extract on the chemiluminescence kinetics of polymorphonuclear leukocytes and on their glycolytic and phagocytic activity.

Water-soluble extracts of cigarette smoke are easily formed in some body compartments, such as saliva or fluid lining alveolar spaces, and can act on both cellular and extracellular compartments. In this paper we have analysed the effect of aqueous smoke extract on some metabolic and functional aspects of polymorphonuclear leukocytes. In particular, the following cellular aspects were studied: chemiluminescence, glycolysis, membrane fluidity and microscopic interaction with zymosan particles. While chemiluminescence and glycolytic activity are highly inhibited, no effect of smoke extract on membrane fluidity was observed. Moreover, the response of luminol-dependent chemiluminescence was significantly delayed, while that of lucigenin-dependent chemiluminescence was anticipated. Furthermore, the phagocytic ability of neutrophils pretreated with aqueous smoke extract was also significantly hindered. All these results might indicate that the finely tuned activity of polymorphonuclear leukocytes is somehow hampered by the aqueous extract of cigarette smoke in a way which makes these cells less effective against bacteria and more noxious towards surrounding tissues.

Orolaryngeal sarcoidosis presenting as obstructive sleep apnoea.

A 53-year-old man was evaluated for snoring, dysphagia for solid foods and difficulty of breathing and a polysomnographic recording was consistent with a diagnosis of obstructive sleep apnoea syndrome (OSAS). A flexible fiberoptic bronchoscopy (FFB) showed the presence of a nodular lesion of the posterior ventral surface of the tongue strictly connected to the left lateral border of the epiglottis. The biopsy specimen taken from the lesion was consistent with sarcoidosis. No involvement of pulmonary parenchyma, lymph nodes or other organs was recognized. After two months of steroid treatment, symptoms disappeared and resolution of the nodular lesion at the FFB and normalization of the polysomnographic recording were observed. This is the first report of orolaryngeal sarcoidosis associated with OSAS as the only clinical presentation of the disease.

Detection by denaturant gradient gel electrophoresis of tumor-specific mutations in biopsies and relative bronchoalveolar lavage fluid from resectable non-small cell lung cancer.

A PCR-denaturant gradient gel electrophoresis (DGGE) method was developed for the detection of p53 and K-ras mutations in primary operable tumors and paired BAL samples of non-small cell lung cancer. Among 36 patients, 9 showed p53 exon V mutations in biopsies and in three paired bronchoalveolar lavage (BAL) specimens with a 33% concordance. Five patients presented p53 exon VI mutations in biopsies and in two paired BALs with a 40% concordance. No mutations were found in p53 exon VII either in biopsies or in paired BAL samples with 100% concordance. Exon VIII mutations were found in six primary tumors and in two BALs with a 33% concordance. Of 36 patients, we detected 7 (19.4%) with K-ras exon I mutations on tumor samples. DGGE analysis of DNA from BAL samples revealed three mutations distributed on K-ras exon I with a 42% overall concordance with respect to tumor tissue. Molecular screening by DGGE of p53-amplified DNA from BAL had cumulative 46.6% sensitivity, 100% specificity, and 77.7% accuracy. DGGE K-ras detection showed 43% sensitivity, 100% specificity, and 88.8% test accuracy. The method proposed demonstrated to be specific, accurate, and at relatively low cost but limited by low sensitivity in detecting the presence of neoplastic cells in patients with resectable non-small cell lung cancer.

Evaluation of a new type of direct digital radiography machine.

OBJECTIVE: To evaluate a recently developed low-dose, large-field, direct digital X-ray scanning system for medical use. METHOD: Radiation dose, image quality, diagnostic capability and clinical utility of the unit were compared with those of conventional radiography. RESULTS: Radiation doses ranged from 3% to 5% of conventional radiographic values, and a mean of 1 line-pair per millimetre could be detected. Ease of use, anatomical coverage and tolerance to patient motion were advantages. However, image quality was inferior to that of conventional radiographs, with limited fine detail visibility and penetration. Only 67 of 156 (42.9%) pathological features seen on conventional radiographs were detected, including 13 of 41 fractures (31.7%) and 11 of 18 pneumothoraces (61.1%). CONCLUSION: Although image quality and diagnostic performance were not ideal, potential roles in triage, foreign body detection and possibly screening were promising. Radiographic factors may have affected sensitivity. This machine demonstrated useful attributes that may, with improvement, be beneficial in the imaging of trauma and other patients.

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.

Contemporaneous acute myeloid leukaemia and sarcoidosis. Report of three cases.

Three cases of contemporaneous acute myeloid leukaemia (AML) and sarcoidosis are described. The possible pathogenic mechanisms concerning their concurrent appearance are discussed: if sarcoidosis impaired T-cell response, it could perhaps predispose the development of AML; alternatively, the development of sarcoidosis during AML may be due to a reaction linked to a diffuse release of tumour antigens with a subsequent formation of a non-caseating granulomata.

Evaluation of pulmonary ventilation and diaphragmatic movement in idiopathic scoliosis using radioaerosol ventilation scintigraphy.

Regional distribution of lung ventilation and diaphragmatic movement were evaluated using a non-invasive scintigraphic method in patients with idiopathic scoliosis. Twenty-four non-smoking patients aged 20 +/- 9 years (mean +/- S.D.), all with a right convex dorsal curve (mean Cobb's angle of 65.1 +/- 26.4 degrees), underwent lung ventilation scintigraphy after inhalation of 99Tcm-labelled human albumin microspheres. The distribution of the inhaled aerosol was assessed and scored based on four scintigraphic patterns, ranging from homogeneous distribution (score = 1) to diffuse severe hypoventilation (score = 4). Diaphragmatic movement, evaluated in 11 of the 24 patients, was assessed using an index (DM-Index) computed for each hemi-diaphragm by the normalization and subtraction of two digital scans obtained during maximal inspiration and expiration respectively. The left lung, situated on the concave side of the scoliotic curve, showed a more uneven distribution of ventilation (scintigraphic score: 2.62 +/- 1.17 vs 1.50 +/- 1.02, P < 0.01) and a reduced hemi-diaphragm movement (DM-Index: 29.2 +/- 4.0 vs 35.9 +/- 2.9, P < 0.001). A significant inverse correlation was found between Cobb's angle and both the right and left DM-Index (r = -0.82 and -0.66 respectively). In a stepwise multiple-regression analysis, the scintigraphic score correlated significantly with the functional index of distribution of inspired gas (IDI) derived from the multiple-breath nitrogen washout curve (P = 0.02). We conclude that lung ventilation scintigraphy provides information on the regional distribution of ventilation and on diaphragmatic movement in idiopathic scoliosis. The pulmonary function derangements in scoliotic patients were mainly localized in the lung on the concave side of the scoliotic curve and were related to the severity of the spinal curvature.

Nasal lavage cytometry in the diagnosis of nonallergic rhinitis with eosinophilia syndrome (NARES).

The nonallergic rhinitis with eosinophilia syndrome (NARES) is a type of chronic rhinitis, characterized by intense (> 20%) eosinophilia of the nasal secretions. In this study, screening for NARES in 81 patients with nonallergic chronic rhinitis was performed using a modified nasal lavage cytometric method. Twenty-one of the 81 investigated individuals (25.9%) showed nasal eosinophilia greater than 20%, therefore being diagnosed as having NARES. No statistical difference in total serum IgE concentration (Prist Pharmacia) was observed between the NARES subjects and those with other forms of chronic rhinitis, confirming the seemingly nonallergic nature of NARES. In 28.6% of these cases the presence of anosmia was detected: in 19.0% of cases with NARES (all subjects complaining of long-lasting symptoms and suffering from anosmia), nasal polyposis coexisted. Our results confirm that nasal lavage cytometry may represent a useful clinical tool in the diagnosis of chronic rhinitis.

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.

Maximal inspiratory pressure in elite soccer players.

The respiratory muscle strength of elite athletes has been assessed only for some competitive sports and different conclusions have been reported. The aim of this study was to evaluate the inspiratory muscle strength in a group of professional soccer players in comparison with a group of sedentary subjects. Maximal Inspiratory Pressure (PImax) was measured both at Functional Residual Capacity (FRC) and at Residual Volume (RV) in 130 subjects: 27 of these were elite soccer players (all males, aged 22 +/- 3 years) and 103 were normal sedentary subjects (77 males and 26 females, aged 44 +/- 19 years). Predictive linear models were produced by a stepwise regression analysis in the whole sample of subjects. Both PImaxFRC and PImaxRV models included female gender and ageing as negative predictors, and Body Mass Index (BMI) as positive predictor of the inspiratory pressures. The model predicting PImaxFRC was slightly more accurate than the model predicting PImaxRV (r-squared: 0.38 vs 0.36, respectively). After adjustment for the variables entered in these models, PImaxFRC and PImaxRV were respectively 1.54 KPa and 1.08 KPa higher in soccer players than in sedentary subjects but this result was statistically significant (p < 0.02) only for PImaxFRC. We conclude that the inspiratory muscle strength is increased in soccer players and PImax measured at FRC seems more sensitive in order to discriminate between subjects with different level of physical activity.

Successful desensitization of a child with desferrioxamine hypersensitivity.

Desferrioxamine is produced by a type of actinomycetes. It reacts with trivalent iron ions and forms a hydrosoluble complex called ferrioxamine B. This complex is able to remove iron from ferrous protein, but not from hemoglobin. This feature permits its use for the treatment of chronic iron accumulation such as that which occurs in thalassemia. Only two cases of successful desensitization to desferrioxamine hypersensitivity have been previously described. This paper describes a case of desensitization in a six-year-old girl with desferrioxamine hypersensitivity. She suffered from Cooley's disease and had received blood transfusions since the age of three months. From the age of four years, the patient was treated with desferrioxamine, which was interrupted after the occurrence of urticaria-angioedema. Skin and patch tests an in vitro lymphocyte transformation test were negative, indicating a pseudoallergic reaction. The desensitization treatment lasted twenty-one days and, afterwards, the patient was able to tolerate desferrioxamine therapy at the dose previously administered (400 mg/day, subcutaneously).

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 Spearman's 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.

Effect of adherence to plastic on peripheral blood monocyte and alveolar macrophage chemiluminescence.

The chemiluminescence of peripheral blood monocytes and alveolar macrophages was determined in the presence of luminol and lucigenin, either before or after the cell adherence to the luminometer curvettes. In the case of monocytes, cell adherence induces an increase of luminol-dependent chemiluminescence and has almost no effect on the lucigenin-dependent chemiluminescence. However, it shows a strong inhibition of the lucigenin-dependent chemiluminescence and almost no effect on luminol-dependent chemiluminescence, in the case of alveolar macrophages. These results show that adhesion to plastic alters the metabolic burst of both monocytes and alveolar macrophages. Although the mechanisms are poorly understood, they seem to be related to the modifications that take place during the differentiation of peripheral monocytes to alveolar macrophages.

Alveolar macrophages from AIDS patients spontaneously produce elevated levels of TNF-alpha in vitro.

In vitro production of TNF-alpha by alveolar macrophages was investigated in 15 AIDS patients with acute interstitial pneumonia and in 4 patients with asymptomatic HIV infection (anti-HIV+) and was compared to that observed in 6 patients with chronic pulmonary disease and in 5 normal controls (undergoing a fiberoptic bronchoscopy for suspected lung malignancy), all 11 HIV negative. Our results show that unstimulated alveolar macrophages of AIDS and anti-HIV+ patients released much more TNF-alpha than subjects with chronic obstructive pulmonary disease or healthy controls did: this overproduction may play a role in the pathogenesis of lung damage infection and particularly in AIDS patients.