Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis.

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.     

Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis

Culture of bronchoalveolar lavage fluid (BALF) is the gold standard for detection of pathogens in the lower airways in cystic fibrosis (CF). However, current culture results do not explain all clinical observations in CF, including negative culture results during pulmonary exacerbation and inflammation in the absence of pathogens. We hypothesize that organisms not routinely identified by culture occur in the CF airway and may contribute to disease. To test this hypothesis we used a culture-independent molecular approach, based on use of rRNA sequence analysis, to assess the bacterial composition of BALF from children with CF and disease controls (DC). Specimens from 42 subjects (28 CF) were examined, and approximately 6,600 total clones were screened to identify 121 species of bacteria. In general, a single rRNA type dominated clone libraries from CF specimens, but not DC. Thirteen CF subjects contained bacteria that are not routinely assessed by culture. In four CF subjects, candidate pathogens were identified and include the anaerobe Prevotella denticola, a Lysobacter sp., and members of the Rickettsiales. The presumptive pathogens Tropheryma whipplei and Granulicatella elegans were identified in cases from the DC group. The presence of unexpected bacteria in CF may explain inflammation without documented pathogens and consequent failure to respond to standard treatment. These results show that molecular techniques provide a broader perspective on airway bacteria than do routine clinical cultures and thus can identify targets for further clinical evaluation.     

Volume-controlled lung lavage in a woman with cystic fibrosis.

A 22-year-old woman with cystic fibrosis was treated by volume-controlled lavage of each of her lungs on two occasions. Following the first lavages, the patient's vital capacity increased by 1.03 liters and her 1-sec forced expiratory volume increased by 0.70 liters/second. Similar improvements, although less pronounced, were noted after both lungs has been lavaged a second time. It is concluded that volume-controlled lung lavage can be of benefit as an adjunct in the treatment of patients with cystic fibrosis.     

Congenital choledochal cyst in an infant with cystic fibrosis

Congenital choledochal cyst is malformation of the biliary ductal system, which rarely occur. We describe here a 4-month old boy, who was referred to our center with respiratory distress and low level consciousness. In physical examination, a mass was detected in right upper quadrant of abdomen. Sonographic examination indicated a cystic structure representing the choledochal cyst. Further evaluation confirmed the diagnosis of cystic fibrosis in this patient. Although choledochal cyst is considered as a rare disease, it is the most frequent malformation of the extrahepatic biliary ducts, which easily could be misdiagnosed.     

Pneumocystis carinii pneumonitis in patients with lung cancer

Pneumocystis carinii pneumonia was histologically documented in five patients with bronchogenic carcinoma. All patients had been treated with combination antineoplastic chemotherapy. Two patients received no corticosteroids, two received no chest radiotherapy, and one received neither radiotherapy nor corticosteroids. This suggests that as more patients with lung cancer are treated with intensive chemotherapy, pulmonary infection with P carinii may become an important differential diagnostic consideration in the presence of pulmonary infiltrates.     

Reversed helper/suppressor T-lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and Pneumocystis carinii pneumonia.

Pneumocystis pneumonia (PCP) usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome (AIDS). Patients with solid tumors represent a very small fraction of the reported cases of PCP. Over an 18-month period, PCP was diagnosed in three patients who had received radiation and chemotherapy for breast cancer. In all three patients, there was no serologic or clinical evidence of AIDS. Direct staining of bronchoalveolar lavage fluid (BAL) revealed Pneumocystis carinii, and cellular analysis of BAL revealed an increased percentage of lymphocytes with reversed helper/inducer:suppressor/cytotoxic T-cell (CD4:CD8) ratio. Because decreased CD4:CD8 ratio in BAL is commonly accepted as findings consistent with hypersensitivity pneumonitis and AIDS, we conclude that similar findings in patients without AIDS are not specific for hypersensitivity pneumonitis, and P. carinii should be ruled out in the appropriate clinical setting.     

High-frequency oscillatory ventilation in an infant with cystic fibrosis and bronchiolitis

Infants with cystic fibrosis (CF) may develop severe respiratory compromise related to viral lower respiratory tract infections due to impaired mucous clearance and plugging of small airways. Consequently air trapping may lead to lung hyperinflation, impaired gas exchange, and respiratory failure. We describe the case of an infant with newly diagnosed CF who developed severe hypercarbic respiratory failure in the setting of viral bronchiolitis successfully treated with high-frequency oscillatory ventilation (HFOV).     

AIDS-related Pneumocystis carinii pneumonia with disappearance of cystic lesions after treatment

A 21-year-old hemophiliac with human immunodeficiency virus (HIV) infection was admitted to our hospital because of bilateral pneumothoraces associated with Pneumocysis carinii pneumonia (PCP). He underwent chest tube drainages and intravenous pentamidine therapy, resulting in clinical improvement. Two months after treatment for PCP, cystic lesions that had existed before treatment disappeared on chest computed tomography. We concluded that Pneumocystis carinii infection might be associated with lung destruction and cyst formation, and that inflammatory exudates in the small bronchioles might act as a ball-valve with subsequent spontaneous pneumothoraces.     

Nasal polyps in cystic fibrosis: clinical endoscopic study with nasal lavage fluid analysis.

STUDY OBJECTIVES: Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group. PATIENTS AND STUDY DESIGN: The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype. RESULTS: The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found. CONCLUSIONS: There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.     

Isolation of an antibacterial peptide from human lung lavage fluid

The contribution of extracellular secretions to the antibacterial defenses of the lungs remains poorly defined. Recent studies have demonstrated that mouse and rabbit bronchoalveolar washings contain a low-molecular-weight peptide that has antibacterial activity against Escherichia coli. In this study we investigated whether a similar peptide could be identified in human secretions. Bronchoalveolar lavage fluid was obtained from normal volunteers and patients with interstitial lung disease or pulmonary alveolar proteinosis. Cellular material and surfactant lipids were removed from the fluid by sequential centrifugations, and the supernatant was fractionated by exclusion filtration to isolate peptides with a molecular weight less than 10,000. Gel filtration chromatography separated the ultrafiltrate into several peaks, the first of which had antibacterial activity against E. coli. This material was further separated into several hydrophilic peaks by reverse-phase high-pressure liquid chromatography (RPHPLC). All samples had similar RPHPLC graphs. Material from the third RPHPLC peak produced an antibacterial effect similar to that produced by the rabbit and mouse peptide.     

Prognostic implications of bronchoalveolar lavage neutrophilia in patients with Pneumocystis carinii pneumonia and AIDS

The clinical records and bronchoalveolar lavage (BAL) cell differential counts were analyzed in 96 patients at risk for Pneumocystis carinii pneumonia (PCP) from human immunodeficiency virus (HIV) infection to determine if this information may be prognostically useful and to identify possible mechanisms of BAL neutrophilia. In 60 patients with PCP, 15 fatalities or episodes of respiratory failure occurred, and 14 of these patients had greater than 5% BAL neutrophils. Only one of 33 patients with PCP and less than 5% BAL neutrophils died. In contrast, there was no correlation between survival and BAL neutrophil percentages in 33 patients who did not have PCP. Three patients with HIV infection without lung disease had normal BAL cell differentials. Intra-alveolar and interstitial leukocytes found in 17 transbronchial lung biopsies in patients with PCP indicate that the alveolar and interstitial compartments of the lung may be the source of BAL neutrophils. Pathologic evidence of increased severity of diffuse alveolar damage to explain BAL neutrophilia was not found. As BAL neutrophil percentages in PCP had both positive and negative predictive value, this information may be useful to stratify therapeutic trials or to identify the patient with PCP who is at high risk of a complicated or fatal outcome.     

Use of a rapid differential stain for identifying Pneumocystis carinii in bronchoalveolar lavage fluid. Diagnostic efficacy in patients with AIDS

Identification of Pneumocystis carinii involves silver stains which require several hours for processing. Diff Quik, a differential stain similar to Wright-Giemsa, requires less than 1 min and reproducibly stains trophozoites and intracystic bodies of P carinii. To determine the utility of DQ for rapid detection of P carinii in BAL fluid, we reviewed DQ-stained slides of 50 BAL samples from 36 patients seropositive for HIV+ who had undergone bronchoscopy with BAL for evaluation of interstitial pulmonary infiltrates. A comparison group of immunocompromised patients with P carinii pneumonia also were reviewed. For HIV+ samples, sensitivity of DQ was 93 and 100 percent for cytopathologists and 75 and 89 percent for pulmonologists. Specificity was 95 percent for each cytopathologist and 100 percent for pulmonologists. For non-HIV+ patients, sensitivity ranged from 22 to 55 percent. Thus, DQ may be useful as a rapid, reliable method to identify P carinii in BAL fluid from HIV+ patients.     

Correlation of bronchoalveolar lavage cell populations with clinical severity of Pneumocystis carinii pneumonia

We correlated bronchoalveolar lavage (BAL) cell populations with clinical course and outcome in 19 patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome. Twelve patients demonstrated an elevated (greater than or equal to 5 percent) BAL combined neutrophil and eosinophil count, which correlated with the magnitude of the alveolar-arterial PO2 gradient. Patients with elevated BAL granulocytes also had significantly higher serum lactate dehydrogenase levels. Three of the four patients who died had the highest percentage of neutrophil counts observed in lavage fluid. Although no patient was thought to have a concurrent bacterial infection, potential pathogens were cultured from the sputum of patients with the most elevated neutrophil counts. Whether BAL granulocytes reflect an inflammatory process analogous to the adult respiratory distress syndrome or signify concomitant bacterial infection remains to be determined. We conclude that BAL granulocytes are associated with more severe respiratory compromise in patients with Pneumocystis carinii pneumonia.     

Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome: an atypical presentation with lung cavitations

The differential diagnosis of lung cavitations is very broad. We report a case of Pneumocystis carinii pneumonia (PCP) with lung cavitations on the chest X-ray in a patient with the acquired immunodeficiency syndrome (AIDS). We discuss the differential diagnosis of such an X-ray pattern and emphasize that multiple cavitations can be a roentgenographic presentation of PCP.     

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience

Liver disease develops in one‐third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.