Luigi Allegra

Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in Children with Community-Acquired Lower Respiratory Tract Infections

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma

We have undertaken cellular and biochemical examination of bronchoalveolar lavage fluid from nonallergic patients with asthma to determine the nature and degree of inflammatory process in symptomatic asthma. Six patients with asthma (mean methacholine provocative concentration causing a 20% fall in FEV1 was 0.26 mg/ml) and six control subjects underwent fiberoptic bronchoscopy with bronchoalveolar wash. The patients with asthma shed a higher number of epithelial cells into lavage fluid than normal control subjects (p less than 0.05). Their lavage fluid also contained increased numbers of neutrophils (p less than 0.025), eosinophils (p less than 0.025), and basophilic cells (p less than 0.025), and increased proportion of activated T cells (p less than 0.05). The basophilic cells were mast cells, as indicated by positive labeling with the monoclonal antibody MCG35. Biochemical analysis of lavage fluid demonstrated exudation of protein molecules in airways of patients with asthma with increased contents of albumin (p less than 0.05) and fibronectin (p less than 0.05). In the lavage fluid of patients with asthma, there were also increased amounts of interleukin-1-beta (IL-1-beta) (p less than 0.025), interleukin-6 (IL-6) (p less than 0.025), and granulocyte-macrophage, colony-stimulating factor (GM-CSF) (p less than 0.05), as compared with lavage fluid of normal control subjects. Immunocytochemical evaluation of lavage cells demonstrated that IL-1-beta, IL-6, and GM-CSF were mostly produced by nonciliated epithelial cells and/or monocytes. IL-1, IL-6, and GM-CSF can prime granulocytes to respond to other stimuli and can promote T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection

Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (> or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment

Background: A study was undertaken to evaluate Chlamydia pneumoniae chronic infection, other respiratory infections, and functional impairment in patients with chronic bronchitis (stage 1) and to examine chronic C pneumoniae infection, rate of acute exacerbations of chronic bronchitis, and rate of C pneumoniae eradication following antibiotic treatment (stage 2). Methods: In the stage 1 study respiratory specimens from 42 patients with steady state chronic bronchitis were analysed for Gram staining, sputum culture, and C pneumoniae DNA detection by nested touchdown polymerase chain reaction (PCR). On the basis of the results of stage 1, a second population of 141 consecutive patients with steady state mild to moderate chronic bronchitis (FEV1 ≥50% predicted) was studied. On admission, at regular intervals, and at exacerbation all patients underwent serological testing for C pneumoniae (microimmunofluorescence) and a nested touchdown PCR to detect C pneumoniae DNA was performed on peripheral blood mononuclear cells (PBMCs). Patients were assessed over a 12 month period. Information regarding the previous 12 months was taken from medical records. Results: Chronic colonisation of the sputum with C pneumoniae was significantly associated with lower FEV1 and greater airway bacterial colonisation. On admission to the stage 2 study, 80 patients were PCR negative and 61 were PCR positive. Over the 2 years a mean (SD) of 1.43 (1.32) acute exacerbations occurred in PCR negative patients and 2.03 (1.21) in PCR positive patients (p<0.01). During the 12 month follow up period 34 PCR positive patients had acute exacerbations and were treated with azithromycin for 6 weeks. Serological evidence of acute C pneumoniae reinfection/reactivation was found in two of the 34 patients. The rate of C pneumoniae DNA clearance from blood following treatment was 29% at follow up. Conclusion: Chronic colonisation with C pneumoniae is associated with a higher rate of exacerbations of chronic bronchitis. Long term treatment is required to obtain clearance of the organism from the blood.

Chlamydia pneumoniae DNA Detection in Peripheral Blood Mononuclear Cells Is Predictive of Vascular Infection

Abdominal aortic aneurysm tissue and peripheral blood mononuclear cells (PBMC) of 41 consecutive subjects undergoing abdominal aortic aneurysm surgery were analyzed by polymerase chain reaction (PCR) for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori DNA. Twenty patients (49%) were positive for C. pneumoniae DNA-16 (39%) in both PBMC and aneurysm tissue, 3 (7.3%) in PBMC only, and 1 (2.4%) in the artery specimen only. Previous exposure to C. pneumoniae was confirmed in 19 (95%) of the 20 PCR positive subjects by C. pneumoniae-specific serology, using the microimmunofluorescence test. None was positive for H. pylori or M. pneumoniae DNA, either in the PBMC or in the artery specimens. In conclusion, carriage of C. pneumoniae DNA is common both in PBMC and in abdominal aortic tissue from patients undergoing abdominal aneurysm surgery. Blood PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the vascular wall.

Comorbidity, Hospitalization, and Mortality in COPD: Results from a Longitudinal Study

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV1, RV, PaO2, and PaCO2 were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV1, PaO2, the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.

Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with pneumonia

The most common clinical signs, host responses and radiographic patterns were studied in 203 Italian children hospitalized for community-acquired pneumonia in order to clarify the role of clinical and radiological characteristics in the diagnosis of Mycoplasma pneumoniae and/or Chlamydia pneumoniae infections. Antibody measurements in paired sera and polymerase chain reaction on nasopharyngeal aspirates were used to establish the diagnoses of acute M. pneumoniae and C. pneumoniae infection, and the aetiologic data were correlated with the clinical, laboratory and radiographic data obtained on admission. No significant association was observed between evidence of M. pneumoniae and/or C. pneumoniae infection and periods of episode during the year, mean age of the study subjects, individual symptoms, physical findings or laboratory test results. Furthermore, no significant correlation was observed in relation to the radiological findings and M. pneumoniae and/or C. pneumoniae infection. This study shows that neither clinical findings nor laboratory parameters distinguished Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection in children with pneumonia. Radiological findings also have a limited capacity to differentiate aetiologic agents. The priorities for future research include the development of rapid, easily accessible and cost-effective diagnostic tests useful for each episode of pneumonia in children.

Bronchial Asthma and Airway Hyperresponsiveness at High Altitude

The mountain climate can modify respiratory function and bronchial responsiveness of asthmatic subjects. Hypoxia, hyperventilation of cold and dry air and physical exertion may worsen asthma or enhance bronchial hyperresponsiveness while a reduction in pollen and pollution may play an important role in reducing bronchial inflammation. At moderate altitude (1,500-2,500 m), the main effect is the absence of allergen and pollutants. We studied bronchial hyperresponsiveness to both hyposmolar aerosol and methacholine at sea level (SL) and at high altitude (HA; 5,050 m) in 11 adult subjects (23-48 years old, 8 atopic, 3 nonatopic) affected by mild asthma. Basal FEV1 at SL and HA were not different (p = 0.09), whereas the decrease in FEV1 induced by the challenge was significantly higher at SL than at HA. (1) Hyposmolar aerosol: at SL the mean FEV1 decreased by 28% from 4.32 to 3.11 liters; at 5,050 m by 7.2% from 4.41 to 4.1 liters (p < 0.001). (2) Methacholine challenge: at SL PD20-FEV1 was 700 micrograms and at HA > 1,600 micrograms (p < 0.005). In 3 asthmatic and 5 nonasthmatic subjects plasma levels of cortisol were also measured. The mean value at SL was 265 nmol and 601 nmol at HA (p < 0.005). We suppose that the reduction in bronchial response might be mainly related to the protective role carried out by the higher levels of cortisol and, as already known, catecholamines.

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan

BackgroundEnvironmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy.MethodsWe collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables.ResultsAn increase in ozone (O3) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2), CO, nitrate dioxide (NO2), and particulate matter (PM10 and PM2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association.ConclusionsExposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

Aspects of bronchial reactivity to prostaglandins and aspirin in asthmatic patients.

The behaviour of bronchial reactivity to PGF2alpha was studied in asthmatic patients under various experimental conditions. Premedication with aminophylline, i.v., and, to a lesser extent, with DSCG afforded a partial protection, while beclomethasone dipropionate was inactive under this point of view. Diftalone, a new non-steroid anti-inflammatory agent, was well tolerated in 9 aspirin-intolerant asthmatic patients, and did not modify the bronchial response to PGF2alpha which was found to be generally lower then that of other aspirin-tolerant asthmatic patients. PGE 1-2 and DSCG prevented the bronchospasm induced by inhalation or ingestion of acetylsalicylic acid in a small group of patients. Good protection was also reached with PGE1-2 in the exercise-induced bronchospasm.