Cytokine profile in lung transplant recipients with Aspergillus spp colonization

We studied cytokine profiles in BAL of LTRs with Aspergillus spp colonization who did not progress to IPA in the absence of antifungal prophylaxis. This was a retrospective, single center case‐control study. BAL samples were analyzed for cytokines. Patients with Aspergillus spp in BAL who did not receive prophylaxis and did not develop IPA were compared to LTRs with Aspergillus spp that received prophylaxis, LTRs with IPA and controls. Twenty‐one patients with Aspergillus colonization who did not develop IPA, seven patients with suspected IPA who received prophylaxis, 4 IPA and 19 controls were included. IPA group had significantly higher levels (median [IQR]) of MIP‐1 beta compared to the Suspected IPA group (5 vs 5 P: 0.03). The Suspected IPA group had significantly higher levels of IL‐12 (11.38 vs 1 P: 0.0001), IL‐1 RA (86.11 vs 23.98 P: 0.0118), IP‐10 (22.47 vs 0.86 P: 0.0151), HGF (40.92 vs 16.82 P: 0.0055), and MIG (169.62 vs 5 P: 0.0005) than Colonization group. We have identified a unique cytokine signature in patients with Aspergillus colonization that do not develop IPA. Our study forms basis for a larger study to use these cytokines profile to identify patients at a lower risk of developing IPA.     

Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

We determined the value of galactomannan (GM) detection in computerized tomography (CT)-based broncho-alveolar lavage (BAL) fluid and serum for the diagnosis of invasive pulmonary aspergillosis (IPA) in haemato-oncological patients with neutropenia. CT of the thorax and BAL were performed systematically at predefined clinical indications. GM was determined by sandwich enzyme-linked immunosorbent assay; the clinicians were unaware of the results. Of 160 patients, 17 patients (10.6%) presented with proven, probable or suspected IPA. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GM detection in CT-based BAL fluid were all 100%. For GM detection in serially sampled serum, the sensitivity was 47%, the specificity 93%, the PPV 73% and the NPV 82%. A non-blinded follow-up study was performed to validate these results. In this study, 22 of 198 patients (11.1%) presented with IPA, and the sensitivity, specificity, PPV and NPV of GM detection in CT-based BAL fluid were 85%, 100%, 100% and 88% respectively. None of BAL fluids obtained after antifungal treatment of 3 d or more were positive. These results indicate that, when CT is used systematically and at an early stage, GM detection in CT-based BAL fluid has a high PPV for diagnosing IPA early in untreated patients.     

Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients

Background  

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking.     

Peripheral blood smear findings in a kidney transplant recipient with disseminated histoplasmosis and elevated Aspergillus galactomannan

We report a case of disseminated histoplasmosis in a renal transplant recipient who presented with a nodular pulmonary lesion and elevated serum and bronchoalveolar lavage (BAL) Aspergillus galatomannan. This almost led to an erroneous diagnosis of invasive aspergillosis since the donor respiratory tract was known to be colonized with Aspergillus terreus. However, distinctive intracelluar Histoplasma yeasts on peripheral blood smear led to early diagnosis and appropriate treatment. The cross‐reactivity between Aspergillus galactomannan and Histoplasma antigen is discussed further.     

Regional differences in bronchoalveolar lavage and thoracic high‐resolution computed tomography results in dyspneic patients with systemic sclerosis

Objective

Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). Although early identification and treatment of alveolitis may prevent deterioration of lung function, the best approach for diagnosing active alveolitis remains controversial. This study was undertaken to investigate the utility of high‐resolution computed tomography (HRCT) of the chest, in comparison with bronchoalveolar lavage (BAL), in the diagnosis of alveolitis in these patients.

Methods

Eighteen patients with SSc and dyspnea were evaluated for ILD by pulmonary function testing and bronchoalveolar lavage (BAL), and 15 of these patients underwent chest HRCT. BAL was performed in either the middle lobe or the lingula, and also in a lower lung segment. Differential cell counts were determined by clinical cytopathology, with retrospective recounting in a blinded manner by a single technician. Active alveolitis was defined as the presence of ≥3.0% polymorphonuclear cells and/or ≥2% eosinophils in BAL fluid. BAL fluids were cultured for bacteria, mycobacteria, and fungi. HRCT scans were evaluated in a blinded manner for ground‐glass opacification and fibrosis in the lavaged lobes.

Results

Nine of the 18 patients had active alveolitis recorded in both lavaged segments, while in 4 patients it was recorded in only 1 segment (lower lobe in 3). Following repeat differential cell counting, 3 patients were reclassified as having active alveolitis and 1 as having no alveolitis. Culture of BAL fluid identified clinically unsuspected infection in 3 patients. For the right middle lung lobe or lingula there was excellent agreement between ground‐glass opacification and the finding of alveolitis on BAL from segments in the same lung regions, but this was not observed for the lower lobes. The correlation between fibrosis on HRCT and the presence of alveolitis on BAL was significant for the lower lobes but not the middle lung fields.

Conclusion

BAL of the middle lobe or lingula may underestimate the presence of active alveolitis. Similarly, while ground‐glass opacification on HRCT accurately predicted alveolitis in the middle lung fields, HRCT did not detect all sites of inflammation and did not identify infectious etiologies. These data suggest that, in addition to HRCT, BAL with lavage, differential cell counting, and culture from at least 2 segments of lung be performed for diagnosing SSc alveolitis.

     

支气管肺泡灌洗液半乳甘露聚糖检测在侵袭性肺曲霉病诊断中的应用价值

侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)好发于免疫功能低下的宿主中,其诊断较困难,病死率高;如能对IPA进行早期诊断并及时给予适当的治疗,能明显改善患者预后.半乳甘露聚糖(galactomannan,GM)是曲霉菌的细胞壁成份,血清GM可用于早期诊断IPA.随着研究的深...     

Diagnosis of invasive pulmonary aspergillosis using polymerase chain reaction-based detection of aspergillus in BAL

STUDY OBJECTIVE: To assess the value of Aspergillus polymerase chain reaction (PCR) test performed on the BAL in diagnosing invasive pulmonary aspergillosis (IPA). DESIGN: Between January 1996 and 1997, we prospectively followed up 249 cancer patients with pulmonary infiltrates suggestive of pneumonia. Bronchoscopy with fungal stains, cultures, and PCR was performed on all patients. PCR was used for the detection of Aspergillus mitochondrial and alkaline protease gene DNA. The PCR products were visualized either directly on polyacrylamide gel or after Southern transfer and probing with specific probes for mitochondrial and alkaline protease DNA. RESULTS: The 249 patients consisted of 10 patients with proven IPA (tissue invasion), 22 patients with probable IPA (microbiologic culture), 18 patients with possible IPA (consistent clinical and radiologic findings), and 199 control patients with no evidence of IPA. PCR positivity was strongly associated with all forms of IPA (p < 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value of PCR were 80%, 93%, 38%, and 99%, respectively, for proven IPA, and 64%, 93%, 52%, and 96%, respectively, for probable IPA. Southern blotting analysis did not improve the diagnostic yield of the PCR test. CONCLUSION: PCR performed on BAL is associated with high specificity and negative predictive value for IPA. The low positive predictive value could be related to the transient colonizing presence of aspergilli in the respiratory tract. The sensitivity correlates with the certainty of the diagnosis based on tissue invasion.     

Real‐world utility of HCV core antigen as an alternative to HCV RNA testing: Implications for viral load and genotype

Following positive serology, the gold standard confirmatory test of hepatitis C virus (HCV) infection is detection of HCV RNA by PCR. We assessed the utility of HCV core antigen testing to identify active infection among those positive for anti‐HCV antibodies, when introduced to routine testing. We identified serum samples that were tested at a single laboratory in Scotland from June 2011to December 2017. Serum samples testing positive for HCV antibodies (HCV Ab positive) followed by reflex HCV core antigen (Ag) testing during the study period were identified. Those patients for whom a PCR test was requested on the baseline sample were also identified. For this group, the sensitivity and specificity of HCV Ag as a diagnostic tool were assessed using HCV PCR as gold standard. In our cohort of 744 patients, we demonstrated a sensitivity of 82.1% (95% CI 77.1%‐86.2%) and a specificity of 99.8% (95% CI 98.6%‐100%). Genotype 3 was associated with increased odds of a false‐negative result (OR = 3.59, 95% CI: 1.32‐9.71), and reduced odds of a false negative were associated with older age (odds ratio (OR)=0.92, 95% CI: 0.88‐0.97 per year) and viral load (OR = 0.10, 95% CI: 0.05‐0.21 per log₁₀ IU/ml). While the implementation of HCV core antigen testing for diagnosis could lead to significant cost savings in national screening programmes, our data suggest that a significant proportion of HCV‐infected individuals may be missed. These findings have implications for HCV diagnosis and determination of viral clearance after treatment, particularly in low‐ and middle‐income regions, where genotype 3 is prevalent.     

Regional differences in bronchoalveolar lavage and thoracic high-resolution computed tomography results in dyspneic patients with systemic sclerosis

OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). Although early identification and treatment of alveolitis may prevent deterioration of lung function, the best approach for diagnosing active alveolitis remains controversial. This study was undertaken to investigate the utility of high-resolution computed tomography (HRCT) of the chest, in comparison with bronchoalveolar lavage (BAL), in the diagnosis of alveolitis in these patients. METHODS: Eighteen patients with SSc and dyspnea were evaluated for ILD by pulmonary function testing and bronchoalveolar lavage (BAL), and 15 of these patients underwent chest HRCT. BAL was performed in either the middle lobe or the lingula, and also in a lower lung segment. Differential cell counts were determined by clinical cytopathology, with retrospective recounting in a blinded manner by a single technician. Active alveolitis was defined as the presence of > or =3.0% polymorphonuclear cells and/or > or =2% eosinophils in BAL fluid. BAL fluids were cultured for bacteria, mycobacteria, and fungi. HRCT scans were evaluated in a blinded manner for ground-glass opacification and fibrosis in the lavaged lobes. RESULTS: Nine of the 18 patients had active alveolitis recorded in both lavaged segments, while in 4 patients it was recorded in only 1 segment (lower lobe in 3). Following repeat differential cell counting, 3 patients were reclassified as having active alveolitis and 1 as having no alveolitis. Culture of BAL fluid identified clinically unsuspected infection in 3 patients. For the right middle lung lobe or lingula there was excellent agreement between ground-glass opacification and the finding of alveolitis on BAL from segments in the same lung regions, but this was not observed for the lower lobes. The correlation between fibrosis on HRCT and the presence of alveolitis on BAL was significant for the lower lobes but not the middle lung fields. CONCLUSION: BAL of the middle lobe or lingula may underestimate the presence of active alveolitis. Similarly, while ground-glass opacification on HRCT accurately predicted alveolitis in the middle lung fields, HRCT did not detect all sites of inflammation and did not identify infectious etiologies. These data suggest that, in addition to HRCT, BAL with lavage, differential cell counting, and culture from at least 2 segments of lung be performed for diagnosing SSc alveolitis.     

Reduced diffusing capacity as an isolated finding in asbestos- and silica-exposed workers

From a cohort of 286 patients referred to an Occupational Medicine Clinic because of exposure to asbestos and/or silica, we identified 53 patients with a reduced diffusing capacity (Dco) (less than 75 percent predicted) as their only abnormality. Specifically, their clinical evaluation, chest roentgenograms, and remaining pulmonary function test results were all normal. These patients were divided into non-smokers (n = 13) and smokers (n = 40). The significance of the isolated reduction in diffusing capacity in these patients (n = 53) was explored with graded exercise testing (n = 19) and bronchoalveolar lavage (BAL) (n = 50). The results obtained from the patients with reduced diffusion were compared with those obtained from comparable smoking (n = 35) and nonsmoking patients (n = 37) in the original cohort who had normal chest roentgenograms and normal results of pulmonary function studies, including normal Dco values (greater than or equal to 75 percent of predicted value). Patients with low diffusion demonstrated a tendency for elevated alveolar to arterial O2 differences both at rest and during exercise, and a significant reduction in exercise capacity (VO2 max) was observed in the smoking patients with reduced diffusion when compared with their smoking counterparts with normal diffusion. All other exercise testing indexes were normal in the study groups and there was no correlation between the percent predicted Dco value and any of the exercise variables. In contrast, BAL revealed significant differences between patient groups. Both the smoking and nonsmoking patient groups with low Dco values had greater numbers of total BAL cells, alveolar macrophages, neutrophils, lymphocytes, and eosinophils in their BAL fluid than did their comparable controls with normal diffusion values. These differences were statistically significant (p less than .05) for total BAL cells and total macrophages in the nonsmoking patients and for total BAL cells, total macrophages, and total lymphocytes in the smoking patients expressed as either the total cell number per BAL or total cells per milliliter of BAL. In contrast to the observed exercise testing results, there was significant and inverse correlation between Dco values and each BAL cell type for all four groups combined as well as nonsmokers alone. The Dco values from smokers were significantly and inversely correlated with total BAL cells and total macrophages. These results suggest that the finding of a reduced Dco may be related to an active inflammatory process in the lung caused by occupational dust exposure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunoglobulin G antineutrophil cytoplasmic antibodies are produced in the respiratory tract of patients with Wegener's granulomatosis

Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology that usually involves the upper and lower respiratory tract and the kidneys. Recently, an association has been made between the presence of serum antineutrophil cytoplasmic antibodies (ANCA) and WG. Because WG frequently involves the lung, we sought to evaluate bronchoalveolar lavage (BAL) fluids obtained from 14 patients with WG for the presence of ANCA. Immunoglobulin (Ig) G ANCA was found in the BAL with the same staining patterns as observed in the serum. Patients with active disease had the highest serum and BAL IgG ANCA titers. IgA or IgM ANCA was not detected in the serum or BAL of these patients. Protein analysis of BAL fluid revealed that patients with active, untreated WG had approximately a fourfold elevation in total protein (41.3 versus 10.5 mg/dl), with a disproportionately greater increase in the ratio of IgG to albumin (BAL IgG index = 1.49, normal = 0.74; p = 0.027). The increase of the IgG index in patients with active WG suggests that local production of IgG ANCA occurs in the lungs.     

Bronchoscopy in the human immunodeficiency virus-infected patient

The spectrum of pulmonary manifestations in patients infected with human immunodeficiency virus (HIV) is broad, including many infectious and noninfectious complications. In the evaluation of an HIV-infected patient with diffuse pulmonary disease a definitive diagnosis is preferred over empiric therapy in most patients. Patients with focal consolidation usually receive empiric treatment for community-acquired pneumonia, with nonresponders undergoing additional diagnostic testing. Bronchoscopy remains a cornerstone in the diagnostic evaluation. A multilobar bronchoalveolar lavage (BAL) is usually sufficient for the diagnosis of Pneumocystis carinii pneumonia (PCP) and avoids the additional complications of hemorrhage and pneumothorax associated with transbronchial biopsy (TBBX). However, TBBX improves the sensitivity for diagnosis of tuberculosis and fungal pneumonias and is necessary to confirm invasive aspergillosis. Definitive criteria for diagnosis of cytomegalovirus pneumonitis have yet to be established, although bronchoscopic specimens usually are used. Tissue confirmation with TBBX is required for the diagnosis of noninfectious disorders such as non-Hodgkin's lymphoma and lymphocytic and nonspecific pneumonitis. Bronchoscopic visualization of typical lesions often is sufficient for the presumptive diagnosis of Kaposi's sarcoma (KS) although the diagnostic yield is enhanced by the detection of human herpes virus 8 in BAL samples.     

Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients

BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.     

Legionnaires' disease in transplant recipients: A 15‐year retrospective study in a tertiary referral center

Legionnaires' disease (LD) can be fatal among high‐risk transplant recipients. To understand the epidemiology of LD, we reviewed 15‐year longitudinal data from a center in Seattle, Washington that cares for both solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients. We identified all laboratory‐confirmed LD and extracted data on species, diagnostic modalities, clinical presentation, management, and outcomes from medical records. Among 32 patients with LD, transplant recipients made up the majority of diagnoses (22, 69%; SOT 10, HCT 12). Approximately 0.8% of transplant recipients who underwent Legionella‐specific testing were positive. Non‐pneumophila Legionella species (LNLP), which are not detected by urinary antigen test, accounted for half the cases, led by Legionella micdadei (32%). The severity and outcome between Legionella pneumophila and LNLP infections were similar (attributed mortality, 36% vs 27%); all LNLP deaths occurred in transplant recipients with L. micdadei. The clinical and radiological features mimicked other opportunistic pathogens; 32% (n=7) were not on empiric treatment at the time of diagnosis. These data add to the emerging literature describing the importance of LD and highlight the need for both routine Legionella testing on transplant recipients with pulmonary findings and empiric Legionella‐active antibiotic therapy.     

Value of ICAM-1 expression and soluble ICAM-1 level as a marker of activity in sarcoidosis

BACKGROUND: The natural course of sarcoidosis is variable, but no single parameter has been generally accepted as a good marker for disease activity. Adhesion molecules are required for the migration of inflammatory cells; thus, they may be markers of activity in sarcoidosis. METHODS: In 16 patients with active sarcoidosis and 11 with inactive disease (10 were male, 17 were female; mean age [-/+ SD], 39.6+/-11.0 years; mean follow-up, 21+/-16 months), the expression of adhesion molecules on cells obtained with BAL (measured by flow cytometry) and the level of soluble intercellular adhesion molecule 1 (sICAM-1) in the serum and BAL fluid (BALF) were measured at the time of diagnosis and during the follow-up. The changes in serum sICAM-1 level and ICAM-1 expression on cells obtained with BAL were compared with the clinical course of the disease. RESULTS: In patients with active disease, the ICAM-1 on alveolar macrophage (AM) (relative linear median fluorescence intensity [RMFI], 3.21+/-1.55) and sICAM-1 levels in serum (575+/-221 ng/mL) and BALF (47.3+/-19.3 ng/mL) were higher than those for patients with inactive disease (RMFI, 1.67+/-0.66; p = 0.0034; serum, 263+/-98.5 ng/mL; p = 0.0001; BALF, 27.5+/-19.0 ng/mL; p = 0.0209). In the patients with active disease, ICAMN-1 on AM and serum sICAM-1 decreased (RMFI, 1.51+/-0.84; 284+/-118 ng/mL, respectively) after steroid therapy, but no significant change was noted in patients with inactive disease. We also found that the initial ICAM-1 on AM and serum sICAM-1 had a significant correlation with the degree of improvement in pulmonary function tests after the therapy. The disease relapsed in four patients after the discontinuation of steroids, and the serum sICAM-1 level was elevated again at the time of relapse. CONCLUSION: Our data suggest that the serum sICAM-1 level and the ICAM-1 expression on AM may be good markers of disease activity and also a predictor of outcome in sarcoidosis.     

The outcome of Chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with <97% identity and similar to those with 98% identity

IGHV gene mutational status has prognostic significance in chronic lymphocytic leukaemia (CLL) but the percentage of mutations that correlates best with clinical outcome remains controversial. We initially studied 558 patients from diagnosis and found significant differences in median time to first treatment (TTFT) among Stage A patients and in overall survival (OS) for the whole cohort, between cases with <97% and 97–98·99% identity and between cases with 97–98·99% and ≥99% identity, when cases from the IGHV3‐21 Stereotype Subset #2 were excluded. A significant difference in progression‐free survival (PFS) and OS between those with <97% and 97–98·99% identity, but not between those with 97–98·99% and ≥99% identity was also observed in a validation cohort comprising 460 patients in the UK CLL4 trial. Cox Regression analyses in the Stage A cohort revealed that a model which incorporated <97%, 97–98·99% and ≥99% identity as subgroups, was a better predictor of TTFT in CLL than using the 98% cut‐off. Multivariate analysis selected the three mutational subgroups as independent predictors of TTFT in Stage A patients, and of OS in the diagnostic cohort. This study highlights that cases with 97% identity should not be considered to have the same prognosis as other cases with mutated IGHV genes defined as <98% identity to germline.     

A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report

We report a case of a 41‐year‐old man presenting with persisting fevers over 2 weeks. The patient had spent 4 weeks in Central America. He was in control of a stable stage II sarcoidosis. Laboratory and various microbiological tests as well as chest radiography led to no diagnosis. Activated sarcoidosis was hypothesized as the most likely diagnosis. However, we considered an infectious process as a differential diagnosis, in detail, the travel history imposed histoplasmosis. Chest‐CT documented localized interstitial consolidations. Bronchoscopy with bronchoalveolar lavage (BAL) and biopsy was performed. Results of BAL fluid, biopsy, distinct sarcoidosis serum markers and a borderline positive histoplasmosis‐serology yielded in a diagnostic dilemma as no distinct diagnosis was drawable. After the patient was already started on a prednisolone trial, the final diagnosis – pulmonary histoplasmosis – could be achieved via positive culture and PCR out of the BAL fluid. This case shows the difficult differentiation between an acute exacerbation of a chronic pulmonary disease and a concomitant infection, which was especially aggravated in this case as the histoplasmosis masqueraded an acute picture of sarcoidosis.     

Contribution of bronchoalveolar lavage to the management of interstitial lung disease

Bronchoalveolar lavage (BAL) is a minimally invasive method for exploring the distal lung. It enables collection of free cellular and acellular material present in the alveoli. Over the last two decades BAL has become a fundamental tool for positive diagnosis of interstitial lung disease and even more for differential diagnosis. It has contributed greatly to the diagnosis of lung infections, particularly in immunosuppressed patients. In the context of non-infectious infiltrative disease, the diagnostic contribution of BAL is limited due to the lack of a specific cell profile. It remains a fundamental tool for the differential diagnosis of idiopathic interstitial pneumonia. With BAL, a number of infectious or tumoral diseases can be ruled out with precision. It is also an important element for the evaluation of possible iatrogenic disease. BAL has transformed the diagnosis of interstitial lung disease and considerably reduced the indications for surgical biopsy.     

Evaluation and outcome of young children with chronic cough

OBJECTIVE: To evaluate the use of an adult-based algorithmic approach to chronic cough in a cohort of children with a history of > 3 weeks of cough and to describe the etiology of chronic cough in this cohort. METHODS: A prospective cohort study of children referred to a tertiary hospital with a history of > 3 weeks of cough between June 2002 and June 2004. All included children followed a pathway of investigation (including flexible bronchoscopy and evaluation of airway cytology via BAL) until diagnosis was made and/or their cough resolved. RESULTS: In our cohort of 108 young children (median age 2.6 years), the majority had wet cough (n = 96; 89%), and BAL fluid samples obtained during bronchoscopy led to a diagnosis in 45.4% (n = 49). The most common final diagnosis was protracted bacterial bronchitis (n = 43; 39.8%). These patients had neutrophil levels on BAL samples that were significantly higher than those in other diagnostic groups (p < 0.0001). Asthma, gastroesophageal reflux disease (GERD), and upper airway cough syndrome (UACS), which are common causes of chronic cough in adults, were found in < 10% of the cohort (n = 10). CONCLUSIONS: The adult-based anatomic pathway, which involves the investigation and treatment of patients with asthma, GERD, and UACS first is largely unsuitable for use in the management of chronic cough in young children as the common etiologies of chronic cough in children are different from those in adults.