An "alternative" clinical course of COPD exacerbation and pulmonary embolism.

Patients with chronic diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and diabetes mellitus, are exposed to particular complications that require a careful diagnostic algorithm. Pulmonary Embolism (PE) in COPD patients often demands an accurate differential diagnosis and a prompt therapeutic intervention. Aspergillus spp. infection comprises a large spectrum of pathological manifestations, depending on immune status and the presence of underlying lung disease. These manifestations may range from invasive pulmonary aspergillosis (IPA) in gravely immunocompromised patients, to chronic necrotizing aspergillosis (CNA) in patients with chronic lung diseases and moderately compromised immune systems. Aspergilloma is generally observed in patients with cavitary lung diseases, and allergic bronchopulmonary aspergillosis (ABPA) is reported in patients with hypersensitivity to Aspergillus antigens. We report a case with pulmonary aspergillosis arisen on a pulmonary infarction after PE in a patient with COPD and diabetes mellitus. To date, report with this clinical evolution was not reported in literature. This report is intended to describe an accurate diagnostic path in a complex overlap of different pathological conditions, highlighting the great importance of differential diagnosis and an appropriate diagnostic algorithm. In addition, open issues on the real diagnostic value of clinical, radiological, and laboratory features for COPD exacerbation, PE and aspergillosis have been discussed.

Treatment of acute exacerbations with non-invasive ventilation in chronic hypercapnic COPD patients with pulmonary hypertension.

BACKGROUND AND OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is a slowly progressive airways disorder characterized by not fully reversible airflow obstruction, often presenting exacerbations of respiratory symptoms requiring hospitalization. Non-Invasive Ventilation (NIV) has been shown to be an effective adjunct to standard medical therapy in the treatment of acute respiratory failure. Secondary pulmonary hypertension leads to a rapid progression of the disease. AIM: To evaluate the effect of NIV treatment in patients with acute exacerbation of COPD, with or without respiratory acidosis, and its effect in patients with pulmonary hypertension. PATIENTS AND METHODS: We enrolled 61 consecutive subjects (M 41; F 20) with COPD admitted to our respiratory ward for acute respiratory exacerbation. Patients were divided into two groups on the basis of arterial pH (group A: 26 individuals with pH <7.35; group B: 35 with pH > or =7.35) and treated with optimal medical therapy (oxygen-therapy, systemic corticosteroids, bronchodilators, antibiotics) and NIV. Moreover, we evaluated functional autonomy thought Six Minute Walking Test (6 mWT), and pulmonary arterial pressure (by transthoracic echocardiography). RESULTS: In group A NIV treatment was associated to a total regression of uncompensated respiratory acidosis (pH 7.36 vs. 7.29). In both groups we observed a significant reduction of PaCO2 (group A: 77.14 +/- 10.4 vs. 45.1 +/- 2.8 mmHg; group B: 70.1 vs. 44 +/- 3.9 mmHg) and an improvement in PaO2 (group A: 51.2 +/- 10.3 vs 84.2 mmHg; group B: 59 +/- vs. 87 +/- 3.3 mmHg). Total average duration of NIV administration was longer in Group A than in Group B (81.14 hours vs 55.83 hours). At the end of NIV treatment, we observed improvement in the autonomy of walking (175.1 meters vs 118.4 meters) in both groups. Patients with severe pulmonary hypertension (PASP > or =55 mmHg) showed a lower reduction of PaCO2 (47.8 vs. 43.7 mmHg) and a minor improvement of arterial pH (7.37 vs. 7.41) compared to patients with a lower value of pulmonary hypertension. CONCLUSIONS: In this study we showed that NIV is useful in patients with or without uncompensated respiratory acidosis, through the improvement of symptoms, blood gases parameters, and walking autonomy. Patients with severe pulmonary hypertension are associated with poorer response to NIV treatment.

A woman with a solitary pulmonary nodule: is it a lung cancer?

BACKGROUND: Solitary pulmonary nodules present a real challenge for physicians. Due to the clinical implications and prognosis of a certain diagnosis, it should be pursued with any cost; a clear definition is not always simple and further investigations are often necessary to exclude the possibility of a malignancy. A diagnostic path must be followed and the clinical hypothesis should be reconsidered on the basis of the new information provided by the tests, always keeping in mind their limits! Sometimes only the surgical resection permits a definitive diagnosis. A 68 year-old non-smoker female with a pulmonary solitary nodule highly suspicious to be malignant at the chest CT, performed a FBS with BAL, negative for neoplastic cells and for infective agents, and a CT guided pulmonary biopsy that was inconclusive. The patient underwent then a video-thoracoscopic atypical lung resection that demonstrated the reactive nature of the lesion, definitely excluding the presence of a malignancy.

A thoracic mass infiltrating the chest wall.

A case of thoracic mass infiltrating the chest wall mimicking a pulmonary invasive neoplasm is reported. Differential diagnosis and characteristic radiological and histological imaging had a decisive role in the case management. Actinomycosis is caused by a gram-positive, filamentous, microaerophilic bacteria. About 15% of the infections caused by Actinomyces involve the thorax. If not promptly diagnosed and treated thoracic actinomycosis may determine contiguous and systemic involvement. Actinomycosis is an anaerobic-to-microaerophilic bacteria and direct identification and isolation are difficult to obtain. In depth discussion diagnostic and therapeutic features are described in this report.

Human neutrophil peptides sputum levels in symptomatic smokers and COPD patients.

BACKGROUND AND OBJECTIVES: Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of airway inflammation and progression towards pulmonary functional impairment, and correlate with the degree of airways obstruction. MATERIALS AND METHODS: We measured, by ELISA tests, HNP concentrations from 37 symptomatic smokers and 34 COPD patients. All participants underwent pulmonary function tests. Sputum samples were collected at the enrolment, and 6 months after smoking cessation. Differences between groups and correlation coefficients between variables were determined using non parametric tests. RESULTS: Sputum HNP concentrations were higher in COPD patients as compared to symptomatic smokers (14 +/- 1.5 microg/ml vs 1.6 +/- 0.4 microg/ml; p < 0.0001). Among COPD patients HNP concentrations were higher in individuals with severe obstruction than in patients with mild to moderate COPD (19.9 +/- 2.3 microg/ml vs 10.3 +/- 0.8 microg/ml, p = 0.003). A negative correlation was observed between HNP levels and FEV1 (rho = -0.38, p = 0.02), and FEV1/FVC (rho = -0.42, p = 0.01). No differences were found in HNP levels before and after 6 months of smoking withdrawal (1.1 microg/ml +/- 0.3 vs 1.1 microg/ml +/- 0.3 for symptomatic smokers, p = 0.9, and 14.4 microg/ml +/- 1 vs 16 microg/ml +/- 1.1 for COPD, p = 0.6). DISCUSSION: Sputum levels of HNP may represent a marker of severity of functional impairment in COPD. Our data support the hypothesis that HNP may have a role in smoking- and COPD-related lung inflammation.

Air pollution ultrafine particles: toxicity beyond the lung.

BACKGROUND: Ultrafine particles or nanoparticles (UFPs or PM0.1) are the fraction of ambient particulates with an aerodynamic diameter smaller than 0.1 microm. Currently UFPs are emerging as the most abundant particulate pollutants in urban and industrial areas, as their exposures have increased dramatically because of anthropogenic sources such as internal combustion engines, power plants, incinerators and many other sources of thermo-degradation. Ultrafine particles have been less studied than PM2.5 and PM10 particulates, mass concentrations of particles smaller than 2.5 and 10 microm, respectively. OBJECTIVE, EVIDENCE AND INFORMATION SOURCES: We examined the current scientific literature about the health effects of ultrafine particles exposure. STATE OF THE ART: UFPs are able to inhibit phagocytosis, and to stimulate inflammatory responses, damaging epithelial cells and potentially gaining access to the interstitium. They could be responsible for consistent reductions in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in patients with asthma. Chronic exposure to UFPs can produce deleterious effects on the lung, also causing oxidative stress and enhancing pro-inflammatory effects in airways of COPD patients. Cardiovascular detrimental consequences due to UFPs exposure have observed in epidemiological studies, and could likely be explained by translocation of UFPs from the respiratory epithelium towards circulation and subsequent toxicity to vascular endothelium; alteration of blood coagulation; triggering of autonomic nervous system reflexes eventually altering the cardiac frequency and function. Once deposited deeply into the lung, UFPs--in contrast to larger-sized particles--appear to access to the blood circulation by different transfer routes and mechanisms, resulting in distribution throughout the body, including the brain, with potential neurotoxic consequences. PERSPECTIVES AND CONCLUSIONS: UFPs represent an area of toxicology of emerging concern. A new concept of environmental medicine would help in understanding not only the environmental mechanisms of disease, but also in developing specific preventive or therapeutic strategies for minimizing the dangerous influence of pollution on health.

Standards of care and clinical predictors in patients hospitalised for a COPD exacerbation--the Italian SOS (Stratification Observational Study).

BACKGROUND AND AIMS: Hospitalisations for chronic obstructive pulmonary disease (COPD) exacerbations are major events in the natural history of the disease in terms of survival, quality of life and risk of further episodes of exacerbation. The aims of study were to evaluate: 1. adherence to recommended standards of care; and 2. clinical factors influencing major outcomes during hospitalisation for an episode of COPD exacerbation and within a 6-month follow-up. METHODS: An observational, prospective study was conducted in 68 centres. Assessment of standards of care included diagnostic procedures (such as pulmonary function tests and microbiology) and management options (such as drug therapies, vaccinations and rehabilitation). Outcome measures relevant to the hospitalisation were: survival, need for mechanical ventilation, and length of stay (LOS). Outcomes at 6-months were: survival, exacerbations and hospitalisations for an exacerbation. Multivariate logistic regression was applied to evaluate the relation between clinical factors and outcomes. RESULTS: 931 patients were enrolled. Only 556 patients (59.7%) were diagnosed COPD and stratified for severity with the support of spirometry (FEV1/VC < or = 0.7) and were considered for outcome analysis. Among treatments, pulmonary rehabilitation and anti-smoking counselling were applied infrequently (14.5 and 8.1% of patients, respectively). Within six months 63 COPD patients (17.7%) had at least one episode of exacerbation prompting a further hospitalisation and 19 died (5.3%). Predictor of mortality was the co-morbidity Charlson index (odds ratio, OR 10.3, p=0.03 CI: 1.25-84.96). A further hospitalisation was predicted by hospitalisation for an exacerbation in the previous 12 months (OR 3.59, p=0.003 CI: 1.54-8.39). CONCLUSIONS: Standards of care were far lower than recommended, in particular 40% of patients were labelled as COPD without spirometry. COPD patients with a second hospitalisation in 12 months for an exacerbation had about 3 times the risk of suffering a new episode and hospitalisation in the following six months.

Methacholine dry powder inhaler as a new tool for bronchial challenge test.

BACKGROUND: The methacholine (MCH) challenge test is performed to detect bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted by inhaling spasmogen substances at increasing doses and measuring FEV1-PD20 variation following the bronchoconstriction evoked. AIM: This paper describes a new method for MCH challenge test using pre-metered respirable powders of MCH at different doses for facilitating test execution. The availability of a series of pre-metered doses gives higher control over aerosolized dose and fine particle fraction (respirable dose), improving the accuracy and repeatability of the test. Dosimetric tests with MCH solution and pre-dosed powder challenge tests were clinically compared. METHODS AND MATERIALS: The inhalation powders were prepared by spray drying of solutions of methacholine, mannitol and hydroxypropylmethylcellulose in which different concentrations of MCH were included. The methacholine powders prepared were carefully characterized in terms of aerodynamic properties. RESULTS: Inhalation powders containing methacholine from 12.5 to 200 microg per metered dose, having a fine particle fraction between 40 and 60%, were prepared using mannitol and cellulose polymer. Eighteen subjects (12 hyperresponsive and six normal) were subjected to both the MCH solution and powder tests in random sequence. No significant differences in FEV1 and PD20 values were found between the challenge tests performed with liquid and powder formulations of methacholine. CONCLUSIONS: Powders of MCH having high respirability of the delivered doses can be prepared by spray drying. They allow for the performance of a challenge test using a dry powder inhaler. The powder dose series can be an alternative to the current dosimetric test with MCH solutions.

Compressor/nebulizers differences in the nebulization of corticosteroids. The CODE study (Corticosteroids and Devices Efficiency).

BACKGROUND: Nebulization is a common method of medical aerosol generation and it is largely used by adults and children all over the world, both for emergency treatment of acute illness and for long-term home treatment of lung diseases. The aim of this study was to determine the differences in nebulization of inhaled corticosteroids among four representative types of compressor/nebulizers. METHODS: Twelve compressor/jet nebulizers from four commercial sources were studied (three for each type): Clenny (MEDEL), Turbo Boy/LC Plus (PARI), Nebula Nuovo/MB5 (MARKOS MEFAR) and Maxaer (ARTSANA) compressor/Sidestream (Medic-Aid Ltd.) nebulizer. We compared the required time for the treatment (nebulization time), output/minutes, compressor pressures, and aerosol characteristics of inhaled corticosteroids: Beclomethasone dipropionate, Flunisolide, Fluticasone propionate and Budesonide. RESULTS: Nebulization Times showed a significant difference between nebulizer and inhaled corticosteroids for Clenny, Turbo Boy, and Maxaer. A considerable difference in the output of nebulized drugs was observed through the compressors/nebulizers. MMAD of all inhaled corticosteroids was significantly different among the four nebulizers. The percentage of particles <5 microm (respirable range) was high for all devices with beclomethasone and budesonide (> 90%), whereas with flunisolide was good only for Clenny (98.8%) and Maxaer (96.3%), and with fluticasone only for Clenny (98%), Turbo Boy (99.1%), and Maxaer (86%). Also percentage of particles <2 microm showed significant variability among the devices. CONCLUSIONS: Our results clearly demonstrate that compressor/nebulizer unit plays a key role in the effectiveness of the treatment during inhaled corticosteroid therapy, and that several differences exist in the performance of the different nebulizers studied. Therefore, the device has the same importance of the compound to reach the best clinical response in the inflammatory diseases of the lower airways.

Lung characteristics in elderly males and females patients with COPD: differences and optimal use of dry powder inhalers (DPIs).

OBJECTIVE: We have measured peak inspiratory flow (PIF), inspiratory capacity (IC), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and other functional parameters in COPD patients to investigate which PIF's patients generate with maximal effort, through three different resistances, representing Diskus, Nexthaler and Turbuhaler. PATIENTS AND METHODS: Forty patients with COPD were enrolled in this study. All patients were examined: pulmonary function tests, including flow/volume spirometry and N2-wash out, were conducted. MIP and MEP were measured. PIF was measured using the In-check DIAL; patients inhaled through the device set for the optimal Turbuhaler resistance, Nexthaler resistance and Diskus resistance. The relationship between lung function parameters and PIF was studied. RESULTS: The mean PIF through Nexthaler resistance was significantly higher than the Turbohaler resistance. We have found a mild correlation between PIF and MIP and between PIF, IC and VC. DISCUSSION: All patients could achieve inspiratory flows > 30 l/min with all inhalers used for the trial. The most interesting result is the mild correlation between MIP and PIF, showing that inspiratory muscle force is probably an important predictor of an adequate inspiratory flow in COPD patients. Many studies confirmed that when using a DPI the inhalation flow is dependent on the resistance of the device and the patient's inspiratory effort. CONCLUSIONS: Inhalation therapy is the mainstay of treatment of patients with COPD. In the last years, significant developments have been achieved in the field of device formulation, but in daily practice, an appropriate inhaler choice should consider not only device related aspects, but also patient's pulmonary function and in particular patient's respiratory muscle strength.

Chronic obstructive pulmonary disease (COPD) exacerbation: impact of comorbidities on length and costs during hospitalization.

OBJECTIVE: A retrospective cohort study was performed, using administrative database of the Local Health Unit Roma-A (LHU RM-A). The included subjects were residing in one of the four districts and were hospitalized for COPD exacerbation in healthcare facilities of the LHU during years 2010-2012. PATIENTS AND METHODS: The aim of the present study is to evaluate the impact of comorbidities, length and costs of hospital stay in patients with COPD exacerbations. Chronic obstructive pulmonary disease (COPD) is often associated with other diseases (cardiovascular diseases, diabetes, metabolic syndrome, chronic renal failure, depression) that can increase risk of mortality and hospitalization. RESULTS: A total of 1890 COPD patients are included in the study. The mean length of hospitalization is 12.25 days (SD ± 10.91), 11.63 days (SD ± 9.76) and 11.91 days (SD ± 9.69) with a mean cost of hospitalization amounting to euro 3683.48 (SD ± 2037.12), 3356.82 (SD ± 1674.86) and 3706.81 (SD ± 2087.72) in 2010, 2011 and 2012 respectively. The presence and number of comorbidities are positively and significantly associated to the length and cost of hospitalization. In particular, patients with cardiovascular diseases or diabetes mellitus associated with other comorbidities present the highest values of hospital stay and cost. The cost and the length of hospitalization were significantly linked to the number of comorbidities. CONCLUSIONS: Comorbidities play an important role in the hospital management of COPD exacerbation, increasing health care costs related to this disease.

Aspiration pneumonia. Pathophysiological aspects, prevention and management. A review.

Aspiration pneumonias occur more frequently than reported and, in many cases, the disease is not recognised. In hospitalised and institutionalised patients with predisposing diseases prompt diagnosis of this complication and correct preventive measures can drastically reduce the worsening of clinical conditions and the deaths due to aspiration pneumonia. Normal airway structure, effective defence mechanisms, and preventive measures are decisive in reducing aspiration episodes. An increased aspiration risk for food, fluids, medications, or secretions may lead to the development of pneumonia. Pneumonia is the most common respiratory complication in all stroke deaths and in mechanical ventilation patients. In addition, the increased incidence of aspiration pneumonia with aging may be a consequence of impairment of swallowing and the cough reflex. Dysphagia, compromised consciousness, invasive procedures, anaesthesia, insufficient oral care, sleep disorders, and vomiting are all risk factors. Aspiration pneumonia includes different characteristic syndromes based on the amount (massive, acute, chronic) and physical character of the aspirated material (acid, infected, lipoid), needing a different therapeutic approach. Chronic patients education and correct health care practices are the keys for preventing the events of aspiration. In patients at risk a clinical and instrumental assessment of dysphagia should be evaluated. Management includes the removal of etiologic factors (drugs, tubes, mobilisation, oral hygiene), supportive care, and in bacterial pneumonias a specific antibiotic therapy for community-acquired or nosocomial events.

Combination therapy in COPD: different response of COPD stages and predictivity of functional parameters.

BACKGROUND: Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) but they do not affect disease progression. FEV1, as single parameter, showed limits in describing the heterogeneity of COPD population. Combination therapy, with long-acting Beta2-agonist and corticosteroid, showed a more beneficial effect on lung function, exacerbations, and health status than single inhaled drug. The aim of this study was to assess, in stable COPD, which stage (mild, moderate, severe) shows the best response after 12 weeks inhaled treatment, and which starting functional parameters show a correlation with the response. METHODS: 170 stable COPD patients (38 mild, 66 moderate, 66 severe) were enrolled. Patients received salmeterol/fluticasone 50/500 microg Metered Dose Inhaler (MDI) bid for 12 weeks. Pulmonary function tests and clinical data were performed. Results were subdivided, on functional and clinical data, in "responders (R)" and "no-responders (NR)". RESULTS: A FEV1 improvement (+ 12% and 200 ml) was achieved in 21 mild, 28 moderate and 17 severe COPD patients, respectively 55.3%, 45.9%, and 30.9% of each group. Statistical analysis of starting functional parameters showed a correlation with the therapeutic response for FEV1/FVC, MEF50 and DLCO/VA% (p < 0.05). CONCLUSIONS: Salmeterol/fluticasone improves FEV1% in mild and moderate more than in severe COPD patients. The study confirmed the difference in response between early and advanced stage. Starting FEV1/FVC and MEF50 were significant predictors in mild and moderate stages, and starting DLCO/VA% resulted a significant predictor in moderate and severe stages.

The influence of ipratropium bromide in the recovery phase of methacholine induced-bronchospasm.

BACKGROUND: The protective effect of Ipratropium Bromide (IB) in the methacholine-induced bronchospasm is well known from some time. The objective of the present study was to assess whether a pretreatment with IB may influence the subsequent phase of methacholine-induced bronchospasm relief. METHODS: Sixteen patients with bronchial hyper-reactivity (PD20 FEV1 < 200 microg) were randomly assigned to three methacholine challenge tests at a 48 to 72 hours interval apart. In the first test IB was inhaled before the challenge (pre-IB), in the second IB was administered soon after the PD20 FEV1 (post-IB), and in the third no treatment was given (control). RESULTS: The pre-IB PD20 FEV1 (695 +/- 587.6 microg) was significantly greater (p < 0.0001) than that of post-IB (82.2 +/- 49.18 microg) and of control (73.9 +/- 41.8 microg). The dose response slope (DRS) (decline percentage of FEV1/cumulative methacholine dose), in pre-IB was greatly lower (p < 0.0001) than that in post-IB and in control. During the bronchospasm relief phase, the increase of FEV1 measured after 5, 10, 15, 30 and 60 minutes from the PD20 FEV1 was significantly greater in post-IB (p < 0.05) compared with the other two conditions. Conversely, the recovery slope (RS) (increase percentage of FEV1 at 60 minutes after PD20 FEV1 x cumulative methacholine dose) was significantly more efficient (p < 0.001) in pre-IB than in post-IB and in control. CONCLUSION: In conclusion, ipratropium bromide confirmed to have a good protective activity against methacholine-induced bronchospasm; the pre-administration of ipratropium bromide showed also a positive effect on the recovery phase.

Early use of non invasive ventilation in patients with amyotrophic lateral sclerosis: what benefits?

OBJECTIVE: The aim of this study was to analyze the efficacy of an early start of NIV in ALS patients, evaluating respiratory and ventilatory parameters. PATIENTS AND METHODS: Functional respiratory parameters and arterial blood gas analysis were evaluated in forty-six patients. All patients were informed about the benefits and possible adverse effects of therapeutic support with NIV and divided in two groups based on the compliance to early start therapy with NIV (Group A) or not (Group B). RESULTS: Among 46 ALS patients consecutively visited in our Unit, we included 20 patients in the Group A and 16 in the Group B. We have emphasized the importance of the early use of NIV stressing the difference between two groups analyzed, particularly in terms of pulmonary function tests and arterial blood gas analysis. Significant correlation was observed between Vital Capacity (VC), Forced Expiratory volume in one second (FEV1), and maximal inspiratory pressures (PImax). CONCLUSIONS: Our study highlights the importance of noninvasive mechanical ventilation as a treatment for ALS patients and also shows the early start of NIV as an important approach in order to postpone the functional decline and the decrease of respiratory muscle strength.

Sarcoidosis at onset of Psoriasis: a common immunopathogenesis. Review and case report.

Sarcoidosis is an inflammatory systemic disease that may present in many different ways. The pathophysiological mechanisms are not still well known, although sarcoidosis results from an exaggerated Th1 immune response. About 30% of sarcoidosis patients may suffer from skin lesions during the course of the disease and, occasionally, psoriasiform lesions have been observed. Sarcoidosis may present associated with other diseases and psoriasis is actually one of them, even though not particularly frequent. Few cases of patients who showed clinical and histological features compatible with both pulmonary sarcoidosis and psoriasis vulgaris have been reported. We report an interesting case of a patient affected by sarcoidosis at the onset of psoriasis and discuss immunopathogenetic mechanisms that can be associated with these conditions. Recent data confirm that sarcoidosis is a Th1/Th17 multisystem disorder. These clarifications may be helpful in the management of the diseases and in identifying patients at risk.

Predictors of outcome for patients with severe respiratory failure requiring non invasive mechanical ventilation.

OBJECTIVE: Failure to identify patients in whom non-invasive ventilation (NIV) would be unsuccessful may cause inappropriate delay in intubation. Aim of this study was to determine predictors of NIV failure. PATIENTS AND METHODS: We retrospectively evaluated COPD patients, undergoing NIV for at least 12h because of hypercapnic acute respiratory failure. Univariable and multivariable analyses were performed on: age, gender, APACHE II and GCS, gas exchange at admission, during NIV and at discharge/death, length of stay. ROC analysis for pH START and APACHE II were performed. RESULTS: Among 201 individuals enrolled, NIV failed in 50. In the logistic regression model only APACHE II was found to have an independent effect on the outcome (p < 0.0001, OR 1.179, 95% CI 1.101-1.263 as quantitative variable; p < 0.0001, OR 3.753, 95% CI 1.798-7.835, as qualitative variable, > 20.5). CONCLUSIONS: APACHE II may be a crucial parameter in predicting NIV failure; further multicentric studies are needed to better define NIV indications.

Lactate dehydrogenase, isoenzyme patterns and cation levels in human breast gross cyst fluid.

In order to investigate the diagnostic and/or prognostic value of total activity and isoenzymatic patterns of lactate dehydrogenase, 24 human breast gross cystic fluids were studied. A comparison of total lactate dehydrogenase activity to the serum level revealed an increased activity in about 63% of the cases examined; moreover, a significant increase in the slow-moving lactate dehydrogenase 4 and 5 isoenzymes was observed in some cyst fluids. The levels of Na+ and K+ concentrations were also analyzed and two classes of cysts were identified: one presenting Na+ and K+ levels similar to those found in extracellular compartment; the other with high K+ and low Na+ levels, characteristic of an intracellular fluid. This latter pattern could indicate an active metabolism of the epithelial cells lining the cysts. This breast cyst fluid also showed increased levels of lactate dehydrogenase 4 and 5 isoenzymes. The correlation between an increased activity of lactate dehydrogenase 4 and 5 isoenzymes and high K+ and low Na+ levels could be the expression of a high biosynthetic activity and of an anaerobic metabolism in some cysts, suggesting the evolution of the breast gross cyst lesion to malignancy. The importance of these observations is discussed.