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.

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.

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.

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.

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.

Abdominal tuberculosis mimicking Crohn's disease: a difficult diagnosis. Report of a case.

Abdominal involvement by tuberculosis as first site of disease is comparatively rare in industrialized countries. The emergence of new groups of patients at risk arouse a particular and due interest. This report describes a case of abdominal tuberculosis with a first diagnosis of Crohn's disease in an immigrant girl from Peru. The diagnosis can be difficult because extrapulmonary tuberculosis is often paucibacillary and the disease may mimic a variety of gastrointestinal disorders.

Brittle asthma.

Brittle asthma is a rare form of severe asthma characterized by a wide variation of Peak Expiratory Flow (PEF), in spite of heavy doses of steroides. Brittle asthmatic patients had very serious and often, life threatening, attacks. Type 1 brittle asthma is characterized by a mantained PEF variability despite therapy, and it affected mostly female, aged between 15 and 55 years. Type 1 is associated to skin prick tests positivity and food intolerance. Several studies have referred a correlation with personality disorders. The patients affected with type 1 have high morbidity, and frequently they have hospital admission for assessment and stabilitation their asthmatic condition. Type 2 brittle asthma is characterized by acute attacks that are very severe and could led to death or mechanical ventilation for respiratory insufficiency. Brittle asthma is very difficult to recognize and to treat. In type 1 brittle asthma, the therapy is based on inhaled and/or oral steroids, and beta2-agonists, used with an inhaler or with subcutaneous infusion. The patients affected with type 1 had to be nearly monitered and treated. Patients affected with type 2 brittle asthma, are mostly free by simptoms, but they have severe attacks that led them to emergency treatment. Brittle asthma is a rare form of severe asthma, that the clinicians may recognize and treat very strictly, because of high morbidity and mortality.

Early protective effects of tiotropium bromide in patients with airways hyperresponsiveness.

Tiotropium is an anticholinergic drug for Chronic Obstructive Pulmonary Disease (COPD) patients, with a peak bronchodilator effect observed after 1.5 to 2 hours and a long duration of action. The aim of our study was to quantify the early protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in asthmatic patients with airway hyperresponsiveness. Ten subjects (7M, 3F), with history of asthma and a baseline FEV(1) (Forced Expiratory Volume 1 sec) > 80% of predicted, were enrolled in the study. Each subject performed three methacholine challenge tests, with a time of 72 hours between each challenge: Test A (methacholine challenge test), and successively, at random, Test B (methacholine 30 minutes after inhaled Tiotropium) and Test C (methacholine 30 minutes after inhaled Placebo). PD20 (Provocative Dose causing a 20% decrease in basal FEV(1) value) was reached to assess airways responsiveness. All the subjects showed in Test A and Test C a mild-moderate airway hyperresponsiveness. In Test B no PD20 was reached at the inhaled maximum dose of methacholine (1600 microg), FEV(1) before tiotropium was 88.6% +/- 4.4, beginning test FEV(1) 92.6% +/- 4.3, end test FEV(1) 85.7% +/- 4.6. Inhaled tiotropium bromide 18 microg has shown a protective effect against methacholine-induced bronchoconstriction in asthmatic patients, with mild-moderate airways hyperresponsiveness, already 30 minutes after its administration.

The smooth muscle and airway hyperresponsiveness.

Airway hyperresponsiveness, excessive airway narrowing caused by stimuli that normally elicit limited or no response, is one of the cardinal features of asthma. The length-dependence of smooth muscle contractility has been recognized for decades, and it forms an essential foundation for many aspects of the physiological regulation of airway contractility in vivo. This review summarizes the structural and functional alterations of airway smooth muscle in asthma and chronic obstructive pulmonary disease, that underlie pathophysiological conditions of airway hyperresponsiveness.

Assessment of right ventricular function by strain rate imaging in chronic obstructive pulmonary disease.

The purpose of the current study was to compare right ventricular (RV) myocardial wall velocities (tissue Doppler imaging) and strain rate imaging (SRI) parameters with conventional echocardiographic indices evaluating RV function in chronic obstructive pulmonary disease (COPD) patients. In total, 39 patients with COPD and 22 healthy subjects were included in the current study. Seventeen patients had pulmonary artery pressure <35 mmHg (group I) and 22 patients had pulmonary artery pressure >35 mmHg (group II). Tissue Doppler imaging, strain and strain rate (SR) values were obtained from RV free wall (FW) and interventricular septum. Respiratory function tests were performed (forced expiratory volume in one second/vital capacity (FEV(1)/VC) and carbon monoxide diffusion lung capacity per unit of alveolar volume (D(L,CO)/V(A))). Strain/SR values were reduced in all segments of group II patients compared with group I patients and controls with lowest values at basal FW site. A significant relationship was shown between peak systolic SR at basal FW site and radionuclide RV ejection fraction. A significant relationship was shown between peak systolic SR at basal FW site and D(L,CO)/V(A) and FEV(1)/VC. In conclusion, in chronic obstructive pulmonary disease patients, strain rate imaging parameters can determine right ventricular dysfunction that is complementary to conventional echocardiographic indices and is correlated with pulmonary hypertension and respiratory function tests.