Quantitative culture of bronchoalveolar lavage fluid in community-acquired lower respiratory tract infections.

To evaluate the diagnostic value of quantitative bacterial culture of bronchoalveolar lavage (BAL) fluid obtained by fibreoptic bronchoscopy, 67 consecutive immunocompetent adult patients admitted to hospital with community-acquired lower respiratory tract infections from September 1997 to May 1998 were investigated. Results were compared to the findings in eight healthy control persons investigated in February 1998. There was no difference between study patients and control persons when quantitative culture of total cumulative bacterial findings or bacteria categorized as members of the oropharyngeal normal flora were compared. The culture of normal flora in bronchial washings probably reflects contamination of the lower airways with secretions from upper arways by the fibreoptic procedure itself, as fractionated sampling showed a 10-fold reduct on in quantitative culture results when a primary bronchial washing was compared to a secondary sampling from the same bronchus in the control group. Twenty-four (36%) of 67 patients were cultured as positive in the study group while all control persons were cultured as negative for bacteria categorized as potential pathogens. With a threshold value for positive culture of 10(4) cfu ml(-1) the specificity of lavage culture of potential pathogenic bacteria in relation to actual lower airway infection was 100%. Therefore, quantitative bacterial culture of potential pathogenic bacteria in BAL fluid is very specific but only positive in about one-third of unselected immunocompetent adult patients with a lower respiratory tract infection.

Intensified microbiological investigations in adult patients admitted to hospital with lower respiratory tract infections.

The objective of this study was to investigate the diagnostic yield of a programme with intensified microbiological investigations in immunocompetent adult patients with lower respiratory tract infections (LRTI). Patients in the study group were included prospectively and consecutively from September 1st 1997 to May 31st 1998 and were compared with a control group from the preceding year. A total of 67 adult patients were included in the study group and they were compared with 122 adult patients in the control group. The study group underwent fibre-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL). Only 7% in the historic control group were discharged with an aetiological diagnosis of their infections; while the diagnostic yield in the study group increased to 51% of patients. In the study group the presence of new infiltrates on chest X-ray increased the detection of a microbiological aetiology from 37% with no infiltrates to 62% with infiltrates and recent antibiotic therapy reduced the detection of a microbiological cause of infection from 61% in 36 patients who had not received antibiotic therapy to 39% in 31 patients who had received recent antibiotic therapy prior to microbiological sampling. Patients in the study group with known aetiology had higher values of inflammatory markers than patients with unknown aetiology. For Streptococcus pneumoniae infection culture and urine antigen detection were complimentary depending on recent antibiotic therapy since seven of eight culture-positive patients had not received antibiotic therapy within 72 h prior to investigation, while all four patients positive for urine antigens from S. pneumoniae had received antibiotic therapy within 72 h of urine sampling. In conclusion intensified microbiologic investigations increase the diagnostic yield from 7% to 51% of patients in the study group with an aetiologic diagnosis. Routine FOB with BAL had no apparent effect on clinical outcome and seems only justified in selected patients with severe LRTI with infiltrates on chest X-ray and signs of severe inflammation where a high diagnostic yield is achieved.

Allergen sensitization and allergen exposure in Greenlander Inuit residing in Denmark and Greenland.

The aim of this study was to estimate the prevalence of allergic sensitization and possible risk factors in a genetically homogenous Inuit population living under widely differing climatic and cultural conditions. A written questionnaire and skin prick test for 10 aeroallergens were obtained from 1119 adult Greenlanders residing in Denmark, Nuuk (main city in Southern Greenland) and Uummannaq (rural settlement in Northern Greenland). Allergen exposure was assessed by pollen counts, questions on pet keeping and counts of house dust mites in dust samples. The overall prevalence of at least one positive skin prick test was 22.8% in Denmark, 10.6% in Nuuk, and 6.4% in Uummannaq. In Denmark, the total birch pollen counts were 40-1000 times higher compared to Nuuk, whereas the grass pollen count was 13-30 times higher in Denmark compared to Nuuk. Dogs were held indoor with a similar frequency in Denmark and Nuuk, but much less frequently in Uummannaq. In Denmark, house dust mites were found in 72% of house holds (>10/0.1 g dust). Less than 15% of households in Greenland had measurable levels of house dust mites. The prevalence of sensitization to aeroallergens in Inuit Greenlanders differed significantly between Denmark, Nuuk and Uummannaq. These findings correlated with the observed differences in population allergen exposure in the three regions. Furthermore, differences in lifestyle factors such as educational level, stress and ethnic self-identification seemed to be associated with the risk of allergic sensitization in Greenland.

A one-year case study of farmers with storage mite allergy.

Four farmers with a positive bronchial challenge test to either L. destructor or T. putrescentiae had bronchial histamine challenge every second month during a year. In the same year, monthly samples of house dust, grain, straw and hay were analyzed for their content of house dust mites and storage mites. The exposure to house dust mites and storage mites differed between farmers. Significant changes in histamine reactivity were found, but no association with time of year or mite counts was observed.

Comparison of two ibuprofen formulations in the treatment of shoulder tendonitis.

In order to compare the efficacy and tolerance of two drug formulations of ibuprofen, conventional tablets 600 mg QID (CI) and sustained-release tablets 1200 mg BID (SRI), a total of 147 patients in 7 centres in Denmark with nontraumatic shoulder pain were included in a double-blind dummy study. Initially all patients received a local injection of corticosteroid and local anaesthetic, and were randomly allocated either drug (CI or SRI) for a period of 3 weeks. Complete relief was recorded from significantly more of the patients in the CI group (21%) than in the SRI group (7%) while a similar number of patients improved viz., 67% of the SRI treated group and 77% of the CI treated group. Based on doctor's assessment improvement in the two groups was equal. 44% of the patients recorded side effects, the number and pattern being the same in the two groups. No serious side effects were recorded. It is concluded that the two treatment regimens can be rated as clinically equivalent.

Potential side effects in patients treated with inhaled corticosteroids and long-acting beta2-agonists.

BACKGROUND: Long-acting-beta-agonists and inhaled corticosteroids are widely used in patients with obstructive lung disease. We determined the occurrence of potential side effects to inhaled steroids and long-acting-beta-agonists in an open post-marketing observational study. METHODS: A total of 158 adult patients treated with long-acting-beta-agonists and inhaled steroids because of asthma or chronic obstructive lung disease were included prospectively in a cross-sectional study from September 2004 through august 2005. A subgroup of 31 patients with minimal disease were observed prospectively after treatment reduction. The frequency and intensity of potential side effects to long-acting-beta-agonists and inhaled corticosteroids were registered on a 10-point visual analogue scale. RESULTS: A total of 131 (83%) reported potential side effects to inhaled steroids. The most frequent were sore (54%) and dry (52%) throat. A total of 114 (72%) patients reported potential side effects to long-acting-beta-agonists. The most frequent were muscle cramps (62%) and muscle twisting (39%). For 5/8 potential side effects their occurrence increased with increased individual dozing. In 31 patients the mean medication with steroids and long-acting-beta-agonists was reduced by 87% and 97.5%, respectively, with side effects reduced by 62% (p<0.001) to inhaled steroids and by 91% (p<0.001) to inhaled long-acting-beta-agonists. CONCLUSIONS: Potential side effects in adult patients to inhaled corticosteroids and long-acting-beta-agonists are very common with increased frequency with increased dozing. Patients are largely unaware of the association. Patients should be better informed, and the results further support tailored dozing to minimum therapy.

Is quantitative PCR for the pneumolysin (ply) gene useful for detection of pneumococcal lower respiratory tract infection?

The pneumolysin (ply) gene is widely used as a target in PCR assays for Streptococcus pneumoniae in respiratory secretions. However, false-positive results with conventional ply-based PCR have been reported. The aim here was to study the performance of a quantitative ply-based PCR for the identification of pneumococcal lower respiratory tract infection (LRTI). In a prospective study, fibreoptic bronchoscopy was performed in 156 hospitalized adult patients with LRTI and 31 controls who underwent bronchoscopy because of suspicion of malignancy. Among the LRTI patients and controls, the quantitative ply-based PCR applied to bronchoalveolar lavage (BAL) fluid was positive at >or=10(3) genome copies/mL in 61% and 71% of the subjects, at >or=10(5) genome copies/mL in 40% and 58% of the subjects, and at >or=10(7) genome copies/mL in 15% and 3.2% of the subjects, respectively. Using BAL fluid culture, blood culture, and/or a urinary antigen test, S. pneumoniae was identified in 19 LRTI patients. As compared with these diagnostic methods used in combination, quantitative ply-based PCR showed sensitivities and specificities of 89% and 43% at a cut-off of 10(3) genome copies/mL, of 84% and 66% at a cut-off of 10(5) genome copies/mL, and of 53% and 90% at a cut-off of 10(7) genome copies/mL, respectively. In conclusion, a high cut-off with the quantitative ply-based PCR was required to reach acceptable specificity. However, as a high cut-off resulted in low sensitivity, quantitative ply-based PCR does not appear to be clinically useful. Quantitative PCR methods for S. pneumoniae using alternative gene targets should be evaluated.

Bacterial colonisation of lower airways in health and chronic lung disease.

BACKGROUND: To evaluate the colonisation rate and type in different groups of patients with chronic lung diseases, bronchial lavage (BL) fluid was investigated for bacteria. METHODS: All patients underwent fibre-optic bronchoscopy as part of routine investigation for remote haemoptysis or nodule investigation. The standard procedure included BL and microbiological culture providing the total number of colony forming units (cfu)/mL and the number of potential pathogenic bacteria (ppb)/mL. Three groups of patients were included: 48 persons had a final diagnosis of no pathology, 53 patients with chronic obstructive pulmonary disease in a stable phase and 32 patients with a final diagnosis of bronchiectasis. RESULTS: The median number of cfu cultured from patients with bronchiectasis was 10(5) cfu/mL compared to 5 10(3) cfu/mL in patients with COPD and 10(4) cfu/mL in persons with no pathology. The ppb colonisation rate varied from 10% in persons with no pathology to 43% in patients diagnosed with chronic obstructive pulmonary disease (COPD) and 63% in patients with bronchiectasis. The most frequent bacteria isolated was Haemophilus influenzae. Colonisation rates were associated with frequencies of respiratory infections; patients with bronchiectasis reported a median of three infections per year, patients with COPD reported one infection per year, and persons without pathology reported 0 infections per year (P < 0.05). Within each group a large patient-to-patient variation was found. CONCLUSIONS: Different groups of patients with chronic pulmonary diseases have very different colonisation rates. Patients with bronchiectasis have the highest colonisation rate. This correlates to the reported frequency of lower respiratory tract infections.

Evaluation of a multiplex PCR for bacterial pathogens applied to bronchoalveolar lavage.

The present study assessed the diagnostic usefulness of a multiplex PCR (mPCR) for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae applied to bronchoalveolar lavage (BAL). Fibreoptic bronchoscopy was performed on 156 hospitalised adult patients with lower respiratory tract infection (LRTI) and 36 controls. BAL fluid was analysed with bacterial culture and mPCR. By conventional diagnostic methods, S. pneumoniae, H. influenzae, M. pneumoniae and C. pneumoniae were aetiological agents in 14, 21, 3.2 and 0% of the LRTI patients, respectively. These pathogens were identified by BAL mPCR in 28, 47, 3.2 and 0.6% of cases, respectively, yielding sensitivities of 86% for S. pneumoniae, 88% for H. influenzae, 100% for M. pneumoniae and 0% for C. pneumoniae, and specificities of 81, 64, 100 and 99% for S. pneumoniae, H. influenzae, M. pneumoniae and C. pneumoniae, respectively. Of the 103 patients who had taken antibiotics prior to bronchoscopy, S. pneumoniae was identified by culture in 2.9% and by mPCR in 31%. Among the controls, mPCR identified S. pneumoniae in 11% and H. influenzae in 39%. In lower respiratory tract infection patients, bronchoalveolar lavage multiplex PCR can be useful for identification of Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydophila pneumoniae. The method appears to be particularly useful in patients treated with antibiotics.

House-dust mites and summer cottages.

BACKGROUND: Estimated indoor climate conditions in unheated summer cottages offers house-dust mites unfavorable temperature and feeding conditions while giving them optimum humidity conditions. We aimed to estimate the exposure level of house-dust mites in summer cottages. METHODS: A total of 37 summer cottages were sampled for house dust and storage mites in three locations and the results compared with samples from 33 patients suspected of house-dust mite allergy and living in ordinary houses. The processed dust samples were investigated by microscopy and exposure levels given as number of mites per 0.1 g dust. RESULTS: The summer cottages were without exception all heavily infested with threefold or higher concentrations of both house dust and storage mites in comparison with ordinary houses. In unheated summer cottages were found tropical high concentrations of house dust and storage mites with a median concentration of house-dust mites in mattress dust of 2000 house-dust mites/g of dust which corresponds to an average of 40 microg allergen/g of mattress dust. CONCLUSIONS: As a probable consequence of high indoor air humidity conditions in unheated summer cottages in winter, dust samples contained threefold or higher concentrations of house dust and storage mites. Indoor humidity conditions thus more than compensated for lack of continuous supply of skin scales from human beings and an unfavorable low indoor air temperature. The uniform high mite exposure in summer cottages is likely to imply disease deterioration in patients already allergic to mites.

House-dust mites and absolute indoor humidity.

The concentration of house-dust mites (Dermatophagoides spp.) was investigated for four seasons in three locations in each of 50 Danish apartments. Simultaneously the absolute humidity was recorded and the previously known correlation between mite counts and indoor humidity was confirmed. It appeared, however, that apartments which had a low absolute indoor humidity in the winter period (due to low household load of water vapour) did not contain noticeable concentrations of house-dust mites in the summer and autumn despite the fact that the indoor absolute humidity in these apartments could be high enough to allow for a high peak-population of mites. Because of this it is suggested that in a temperate climate avoidance measures against house-dust mites should be supplemented at least by a drying out period in the winter, when this process is convenient to perform because of the low outdoor absolute humidity.

Preventive measures in mite asthma. A controlled trial.

To evaluate the effect of preventive measures 46 patients, all allergic to house-dust mites (Dermatophagoides spp.), were randomly allocated to a study and a control group. According to the patients' subjective recordings of symptom score and use of medicine, compared with the control group, the study group had improved. There was, however, no improvement when comparing the objective recordings of morning and evening peak flow and use of medicine, and it is concluded that the preventive measures in this programme are not very effective for patients allergic to house-dust mites. The reduction in indoor humidity in the study group was limited and, as a high indoor humidity is the cause of huge populations of house-dust mites in homes, it is emphasized that future programmes of preventive measures should focus more on damp problems, particularly those related to bad housing construction.

Mite asthma and residency. A case-control study on the impact of exposure to house-dust mites in dwellings.

The occurrence of mites in house dust from the homes of 25 patients with newly diagnosed house-dust mite asthma was much greater than that in the house dust from homes of 75 randomly selected matched control subjects. The difference in exposure corresponded to a relative risk of about 7.0, and a clear dose-response relationship could be demonstrated. The 25 patients lived in older and more humid houses than the control subjects did, which explains the greater number of house-dust mites found and suggests possibilities for and the necessity of introducing hygienic standards for the indoor environment as a measure of primary prevention in house-dust mite allergy.

Epidemiology of house-dust mites.

Available epidemiologic data on the occurrence of house-dust mites in dwellings demonstrates a clear association between increased indoor air humidity and the increased occurrence of house-dust mites in house dust. Furthermore, in temperate climates, there is a threshold level of indoor air humidity of 7 g/kg (45% relative humidity at usual indoor air temperatures). Indoor air humidities below this level for extended periods will eradicate house-dust mites from dwellings. A reduction in inhabitant exposure to house-dust mites is implemented by reduction of indoor air humidity by controlled mechanical ventilation. Individual ventilation levels are estimated from the actual size of house, number of inhabitants, and average outdoor air humidity in winter. In contrast, more humid areas of the world with average outdoor humidities above 6-7 g/kg in winter will support uniformly large populations of house-dust mites, and reductions in indoor air humidity will have a comparatively minor effect on the occurrence of house-dust mites. Present-day building of energy-efficient houses with increased sealing of the building envelope, paralleled by a similar renovation of older houses, has increased indoor air humidity and is probably the cause of the almost fourfold increase in the occurrence of house-dust mites in Danish dwellings.