Bronchoalveolar Lavage Lymphocyte Counts Research Articles

The efficacy of N-acetylcysteine in decreasing airway inflammation and mucus accumulation in horses with 18 hours of head confinement.

During transportation many horses develop post-transportation infection, which can be life-threatening and end their sport career. Preventing mucus accumulation and inflammation during transportation is vital, emphasizing the need for effective strategies to enhance overall horse health welfare. Assess the impact of N-acetylcysteine (NAC) on mucus accumulation and inflammation in horses subjected to 18 hours of head confinement. Six healthy crossbred horses, 5.3 ± 2.1 years of age and weighing 387 ± 30 kg. Prospective placebo-controlled cross-over design study. The horses' heads were restrained in their stalls for a period of 18 hours. They were studied under 4 conditions: Not confined (NC): before head confinement, placebo (P), and confined head (CH): 18 hours of head confinement without treatment, and N-Acetylcysteine (NAC): 18 hours of head confinement treated with NAC before confinement (15 mg/kg/day NAC PO for 3 days). Bronchoalveolar lavage (BAL) was performed in each condition. Mucus accumulation along the trachea was evaluated by endoscopy. Endoscopic scores were significantly different between CH and other conditions, whereas no significant differences were found among NC, P, and NAC. The BAL cell count (34 291 ± 2624 cells/μL), neutrophil and lymphocyte count (18 601 ± 3193 cells/μL and 3337.4 ± 593 cells/μL, respectively) in CH were significantly higher compared to NAC. Neutrophil percentage was significantly higher in CH (53.8 ± 8%) compared to horses that received NAC (20.08 ± 8%). Conversely, in comparison to NAC (66.33 ± 9%), the percentage of macrophages was significantly lower in CH (35.7 ± 10%). N-acetylcysteine was found to significantly decrease mucus accumulation and inflammatory cell counts in horses with head confinement.

Real-Life Diagnostic Performance of the Hypersensitivity Pneumonitis Guidelines: A Multicenter Cohort Study.

Hypersensitivity pneumonitis (HP) is a heterogeneous interstitial lung disease (ILD) that may be difficult to confidently diagnose. Recently, the 2020 ATS/JRS/ALAT HP diagnostic guidelines were published, yet data validating their performance in real-life settings are scarce. We aimed to assess the diagnostic performance of the HP guidelines compared to the gold-standard multidisciplinary discussion (MDD). For this purpose, we included consecutive ILD patients that underwent diagnostic bronchoscopy between 2017 and 2020 in three large medical centers. Four diagnostic factors (antigen exposure history, chest computed tomography pattern, bronchoalveolar lavage lymphocyte count, and histology results) were used to assign guidelines-based HP diagnostic confidence levels for each patient. A sensitivity analysis was performed, with MDD diagnosis as the reference standard. Overall, 213 ILD patients were included, 45 (21%) with an MDD diagnosis of HP. The guidelines' moderate (≥70%) confidence threshold produced optimal performance with 73% sensitivity for HP, 89% specificity, and a J-index of 0.62. The area under the receiver operating characteristic curve (AUC) for a correct guidelines-based diagnosis was 0.86. The guidelines had better performance for non-fibrotic than fibrotic HP (AUC 0.92 vs. 0.82). All diagnostic factors, except bronchoalveolar lavage lymphocyte count, were independent predictors for MDD diagnosis of HP in a multivariate analysis. In conclusion, the HP guidelines exhibited a good diagnostic performance compared to MDD diagnosis in real-life setting.

Correlation of bronchoalveolar lavage lymphocyte count with the extent of lung fibrosis and with plethysmographic lung volumes in patients with newly recognized hypersensitivity pneumonitis.

IntroductionHypersensitivity pneumonitis (HP) is an increasingly recognized interstitial lung disease, presenting with elevated total cell counts and high percentage of lymphocytes in bronchoalveolar lavage fluid (BALF). Despite many publications, there is no consensus in the literature concerning BALF cellular composition in patients with prolonged course of HP.AimThe aim of the present retrospective study was to investigate the influence of disease duration, smoking habits, and the extent of lung fibrosis on BALF cells’ population in patients with newly recognized HP.Material and methodsIn total, 94 patients (49 females, 45 males), mean age 52 (±12) years, with HP recognized according to recently proposed criteria, were enrolled into the present study. Chest CT scans were retrospectively reviewed by two independent radiologists. BALF evaluation was performed as a part of routine diagnostics according to recent recommendations.ResultsPercentage of lymphocytes in BALF was significantly lower in patients with lung fibrosis (stage 1 and 2) comparing to those without lung fibrosis (stage 0). Significant correlation was also found between the percentage of BALF lymphocytes and plethysmographic lung volumes, but not with lung transfer capacity for carbon monoxide (TLCO% pred). Smoking did not influence BALF results in our study group.ConclusionsBALF lymphocytosis correlated with the presence and the extent of lung fibrosis on chest CT as well as with plethysmographic lung volumes but did not with TLCO and smoking habits in newly recognized HP pneumonitis.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia.

BackgroundTrimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients.Materials and MethodsNinety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group).ResultsAmong the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis.ConclusionThis study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Airway and serum biochemical correlates of refractory neutrophilic asthma

BackgroundDespite progress in the diagnosis and management of asthma, many patients have poorly controlled or refractory asthma (RA). The mechanism of this RA is not well understood.ObjectiveWe sought to explore the relationship between neutrophils and other biomarkers of RA.MethodSixty patients with RA, 30 patients with nonrefractory asthma (NRA), and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest computed tomography, and bronchoscopy with bronchoalveolar lavage (BAL). We analyzed BAL fluid and serum for a total of 244 biomolecules using a multiplex assay and correlated them with clinical and other laboratory parameters.ResultsRA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL fluid neutrophil and lymphocyte counts but not eosinophil counts. BAL fluid neutrophil counts negatively and positively correlated with forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL fluid and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL fluid neutrophil counts. BAL fluid from 40% of patients with RA was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in levels of select biomarkers of inflammation in the serum, suggesting the presence of systemic inflammation.ConclusionsRA was associated with increased numbers of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of patients with RA, which likely contributed to neutrophilic inflammation. A subgroup of patients with noninfected neutrophilic RA was associated with systemic inflammation.

Is bronchoalveolar lavage a game changer in the diagnosis of interstitial lung disease?

Bronchoalveolar lavage (BAL) is a technique that is in use since the advent of the rigid bronchoscope and subsequently it was also utilized with the flexible bronchoscope. It was evolved as a therapeutic modality to drain purulent secretions and also for treatment of diseases like alveolar proteinosis.[1] However, much later low volume BAL was used to diagnose diseases such as malignancy, infection, and interstitial lung disease (ILD). ILD are a group of diseases that present with exertional dyspnea, dry cough, and infiltrates in bilateral lung fields, which are evident on chest radiography and high resolution computed tomography (HRCT) of the chest. There have been numerous tests to diagnose this perplexing disease. The gold standard for diagnosis is surgical lung biopsy.[2] However, with the advent of HRCT of the chest, it has been possible to identify and classify ILD's through these noninvasive means. In early disease, however, diagnosis is difficult and in such cases BAL may be helpful. The role of BAL in the diagnosis of ILD had been debatable until the American Thoracic Society (ATS) issued guidelines to define the methodology, processing, and use of BAL in the diagnosis of ILD in 2012.[3] The guidelines stated that BAL may be a useful adjunct to other diagnostic modalities rather than being a stand-alone diagnostic test. The site for BAL should be decided by the part of the lung involved with disease process on HRCT rather than the conventional BAL sites such as the right middle lobe or lingula. Differential cellular count should be performed on the BAL sample and should include measurement of lymphocytes, neutrophils, macrophages, and eosinophils. Lymphocyte subset analysis is not routinely recommended in all ILD cases. BAL analysis may also exclude diseases such as malignancy, infections, and certain rare diseases like pulmonary alveolar proteinosis. In the current issue of the journal, Palaniswamy et al.[4] diagnosed fifty cases of ILD on the basis of HRCT and then performed BAL in the same. The paper highlights few important issues. The first, BAL is a relatively safe test which can be performed in a suspected case of ILD. The BAL findings may not be pathogonomic for a certain type of ILD, but they may help confirm or exclude a certain disease diagnosis. For example, a patient who was suspected to have idiopathic pulmonary fibrosis (IPF) on HRCT underwent bronchoscopy and BAL analysis, which subsequently revealed histiocytes. Thus, the diagnosis was revised to chronic langerhan cell histiocytosis rather than IPF. This supports a previous study conducted by Ohshimo et al. in which they found that 8% of patients diagnosed as usual interstitial pneumonia pattern on HRCT thorax may have a different diagnosis when evaluated with BAL analysis.[5] The second issue that has been highlighted in the current paper is that BAL may help in identifying acute exacerbations and super-added infections. These may be treated with a systemic course of steroids and antibiotics, respectively. The study has certain limitations that including lack of gold standards such as surgical lung biopsies and non inclusion of ILD patients with inconclusive HRCT. The ATS recommends performing BAL in all patients of ILD with nondiagnostic HRCT and these may be the patients who may be candidates of surgical lung biopsy subsequently. A BAL lymphocyte count of >25% is suggestive of nonspecific interstitial pneumonia, hypersensitivity pneumonitis (HP), or sarcoidosis.[56] An eosinophil percentage of more than 25% is highly diagnostic of eosinophilic pneumonia.[6] Similarly, a BAL neutrophil level of >50% is suggestive of acute interstitial pneumonia or acute infection.[6] These BAL abnormalities may also be seen in other non-ILD conditions such as bronchiolitis, asthma, or allergic bronchopulmonary aspergillosis. Thus, BAL findings should be cautiously interpreted and correlated with clinical and HRCT findings. Furthermore, it has been shown that BAL findings may alter once fibrosis sets in diseases like HP.[7] In conclusion, BAL analysis subsequent to HRCT evaluation is a useful test to confirm the diagnosis, exclude acute exacerbation and super-added infections in cases of ILD. BAL findings should however be carefully interpreted in context to the clinical and radiological findings.

Additive anti-allergic effects of anti-interleukin-33 and anti-Siglec-F treatments in a murine model of allergic asthma.

BackgroundAnti-interleukin-33 (anti-IL-33) and anti-Siglec-F antibodies have potent anti-allergic effects on murine allergic asthma and rhinitis and induce eosinophil apoptosis.ObjectiveWe aimed to determine whether post-sensitization with anti-IL-33/anti-Siglec-F treatments exhibited more potent effects compared to individual treatments in a murine allergic asthma model.Material and methodsTwenty-five BALB/c mice were separated into five groups (n = 5): Group A (control), Group B (ovalbumin [OVA] challenge), Group C (OVA + anti-IL-33), Group D (OVA + anti-Siglec-F), and Group E (OVA + anti-IL-33 + anti-Siglec-F). Serum total/ OVA-specific IgE, bronchoalveolar lavage (BAL) inflammatory cells and cytokines (IL-4 and IL-5), histopathological lung properties, and airway hyperreactivity were compared.ResultsOvalbumin challenge induced strong immune and inflammatory responses with > 6-fold IgE level increases; 10- to 25-fold BAL eosinophil, neutrophil, and lymphocyte count increases; and > 1.5-fold IL-4 and IL-5 level increases (p < 0.05). Whereas anti-IL-33 reduced neutrophil counts, anti-Siglec-F and anti-IL-33/anti-Siglec-F reduced both eosinophil and neutrophil counts (p < 0.05). Individual treatments reduced OVA-mediated bronchiolar infiltration by 50% (p <0.05). Ovalbumin challenge increased airway hyperreactivity by 4-fold (Group B; 2000.0 ±671.8% increase in Penh) compared to controls (Group A; 445.7 ±33.5% increase in Penh) (p = 0.016). The anti-IL-33 (Group C: 1579.4 ±973.6% increase in Penh) and anti-Siglec-F (Group D: 930.4 ±236.5%) groups demonstrated significantly reduced hyperreactivity (p = 0.029). Anti-IL-33/anti-Siglec-F therapy showed synergism towards neutrophil counts, IL-5 concentrations, bronchial infiltration, and hyperreactivity (p < 0.05).ConclusionsCombination treatment with anti-IL-33/anti-Siglec-F had more potent anti-allergic effects, reducing eosinophilic infiltration through their additive effects in a murine allergic asthma model.

Acidic mammalian chitinase is not a critical target for allergic airway disease in mice

The expression of acidic mammalian chitinase (AMCase) is associated with Th2-driven respiratory disorders. To investigate the potentially pathological role of AMCase in allergic airway disease (AAD), we sensitized and challenged mice with ovalbumin or a combination of house dust mite (HDM) plus cockroach allergen. These mice were treated or not treated with small molecule inhibitors of AMCase, which significantly reduced allergen-induced chitinolytic activity in the airways, but exerted no apparent effect on pulmonary inflammation per se. Transgenic and AMCase-deficient mice were also submitted to protocols of allergen sensitization and challenge, yet we found little or no difference in the pattern of AAD between mutant mice and wild-type (WT) control mice. In a separate model, where mice were challenged only with intratracheal instillations of HDM without adjuvant, total bronchoalveolar lavage (BAL) cellularity, inflammatory infiltrates in lung tissues, and lung mechanics remained comparable between AMCase-deficient mice and WT control mice. However BAL neutrophil and lymphocyte counts were significantly increased in AMCase-deficient mice, whereas concentrations in BAL of IL-13 were significantly decreased compared with WT control mice. These results indicate that, although exposure to allergen stimulates the expression of AMCase and increased chitinolytic activity in murine airways, the overexpression or inhibition of AMCase exerts only a subtle impact on AAD. Conversely, the increased numbers of neutrophils and lymphocytes in BAL and the decreased concentrations of IL-13 in AMCase-deficient mice challenged intratracheally with HDM indicate that AMCase contributes to the Th1/Th2 balance in the lungs. This finding may be of particular relevance to patients with asthma and increased airway neutrophilia.

Clinical characteristic analysis of 96 cases of hypersensitivity pneumonitis

To improve understanding of the clinical characteristics and diagnosis of hypersensitivity pneumonitis (HP). We retrospectively analyzed the clinical data, including clinical symptoms, laboratory tests, exposure, pulmonary function tests, chest CT imaging and cytological classification of bronchoalveolar lavage (BAL) of 96 patients with HP from Jan 2001 to Jun 2011 in Peking Union Medical College Hospital. We divided the patients into 2 groups: a pathologically-confirmed group and a clinically-suspected group. There were 58 females and 41 males. The median age at the diagnosis was 53 years. The most common exposures were low-molecular-weight chemicals (42.7%) and animal proteins (37.5%). Common clinical symptoms included dyspnea on exertion (90.6%) and cough (76.0%). Pulmonary function test showed diffusion abnormality (73.5%) and restrictive ventilatory impairment (59.7%). Chest CT scan revealed patchy or diffuse bilateral ground-glass opacities (64.6%), centrilobular nodules (21.9%), and air trapping (15.6%). Reticulation (45.8%), traction bronchiectasis (21.9%) and honeycombing(9.4%) were present in chronic HP. BAL lymphocyte counts > 0.2 and CD4/CD8 < 0.9 were more commonly seen in patients with a disease course of less than 1 year. The pathologically-confirmed group and the clinically-suspected group shared many similar characteristics including age at diagnosis, gender, clinical manifestation, pulmonary function impairments and imaging findings, but significant differences existed in certain parameters. In the pathologically- confirmed group, the duration of disease was longer (24 months vs 6 months, Z = -2.492, P = 0.013) and clubbed fingers were more common (23.4% vs 8.2%, χ(2) = 4.227, P = 0.040). Diffusion abnormality was present in more patients of this group (90.7% vs 44.0%, χ(2) = 35.219, P < 0.01). By CT scan, reticulation, traction bronchiectasis and honeycombing (57.5% vs 26.5%, χ(2) = 9.434, P < 0.01) were more evident as compared to the clinically-suspected group. The value of transbronchial lung biopsy for diagnosing HP was limited, with a positive result of only 8.2%. Surgical lung biopsy was needed in uncertain cases. The diagnosis of HP was difficult. In some cases a clinical diagnosis can be made by combination of history of exposure, CT manifestations and cell classification of BAL. For atypical cases a multi-disciplinary approach including pathologists, radiologists and pulmonologists is needed.

Acidic Mammalian Chitinase Is Not a Critical Target for Allergic Airway Disease

The expression of acidic mammalian chitinase (AMCase) is associated with Th2-driven respiratory disorders. To investigate the potentially pathological role of AMCase in allergic airway disease (AAD), we sensitized and challenged mice with ovalbumin or a combination of house dust mite (HDM) plus cockroach allergen. These mice were treated or not treated with small molecule inhibitors of AMCase, which significantly reduced allergen-induced chitinolytic activity in the airways, but exerted no apparent effect on pulmonary inflammation per se. Transgenic and AMCase-deficient mice were also submitted to protocols of allergen sensitization and challenge, yet we found little or no difference in the pattern of AAD between mutant mice and wild-type (WT) control mice. In a separate model, where mice were challenged only with intratracheal instillations of HDM without adjuvant, total bronchoalveolar lavage (BAL) cellularity, inflammatory infiltrates in lung tissues, and lung mechanics remained comparable between AMCase-deficient mice and WT control mice. However BAL neutrophil and lymphocyte counts were significantly increased in AMCase-deficient mice, whereas concentrations in BAL of IL-13 were significantly decreased compared with WT control mice. These results indicate that, although exposure to allergen stimulates the expression of AMCase and increased chitinolytic activity in murine airways, the overexpression or inhibition of AMCase exerts only a subtle impact on AAD. Conversely, the increased numbers of neutrophils and lymphocytes in BAL and the decreased concentrations of IL-13 in AMCase-deficient mice challenged intratracheally with HDM indicate that AMCase contributes to the Th1/Th2 balance in the lungs. This finding may be of particular relevance to patients with asthma and increased airway neutrophilia.

Extrinsic allergic alveolitis: comparative study of the bronchoalveolar lavage profiles and radiological presentation

Introduction: Extrinsic allergic alveolitis (EAA) is an immunologically mediated interstitial lung disease. The abnormalities in the bronchoalveolar lavage (BAL) fluid cell counts are almost always seen in patients with EAA...

Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias

The purpose of this study was to assess the role of bronchoalveolar lavage (BAL) in differentiating usual interstitial pneumonia (UIP) from non-specific interstitial pneumonia (NSIP) and in predicting the prognosis in fibrotic idiopathic interstitial pneumonia (IIP). A retrospective review of 122 patients (age 58+/-8 years, 70 male) with UIP (n=87) and NSIP (n=35) was carried out. Prior to surgical lung biopsy, all of them underwent BAL and high-resolution-computed tomography (HRCT) of the chest. Neutrophil count in BAL fluid was higher in UIP (7.0%) than NSIP (3.0%) (P=0.027). In contrast, BAL lymphocyte count was significantly higher in NSIP (29.0%) than UIP (5.5%) (P<0.0001). In 62 patients whose HRCT findings were atypical for UIP, BAL lymphocytosis was more frequently observed in NSIP (20/33) than UIP (4/29) (P<0.001) and the absence of BAL lymphocytosis suggested a diagnosis of UIP rather than NSIP (odds ratio 12.7, P<0.001). Pathologic diagnosis of NSIP was the only independent factor predicting a longer survival of our patients (median follow-up 21 months) (hazard ratio (HR) 0.035, P=0.005). When NSIP was not included in the survival analysis, higher BAL lymphocyte count was the only independent predictor of a longer survival (HR 0.909, P=0.029). BAL is an useful non-invasive tool in fibrotic IIP, not only for excluding a variety of specific non-IIP diseases but also for narrowing the differential diagnosis and predicting the prognosis in the absence of the histopathologic diagnosis.

Depleting anti-CD4 monoclonal antibody inhibits the bronchial late phase response in a mouse model of asthma

Rationale We aimed to investigate the role of CD4+ cells in the bronchial late phase response (LPR) in a mouse-model of asthma, characterized by an allergen-specific LPR. Methods Male Balb/C mice (6–8 weeks) were sensitized by ovalbumin (OVA) (i.p.) on alternate days from d1 till d13. The challenge phase comprised daily nebulizations of OVA from d33 till d40. On d47 500ul PBS (control) or 100 μg GK1.5 (depleting anti-CD4 monoclonal antibody) was administered i.p. The LPR was induced by nebulized OVA on d50. The enhanced pause (PenH) was measured every 30 seconds during 6 hours by body plethysmography. The mice were sacrificed for flowcytometric analysis of whole blood, differential cell counts and cytokine measurements on broncho-alveolar lavage (BAL), and for RT-PCR on lung tissue. Results Within the CD3+ population, GK1.5 diminished the CD4+ cells by more than 90%. In the control mice an LPR could be induced with PenH peaking at 240 min whereas in the GK1.5 group the LPR was inhibited. The area under the curve of the PenH/time curve was lower in the GK1.5 mice compared to the control mice (p=0.03, t-test). BAL lymphocyte, monocyte and eosinophil counts were lower in the GK1.5 group (p=0.03, p=0.03 and p=0.02 respectively, t-test). BAL IFN-γ was lower in the GK1.5 group (p=0.02, t-test). IL-4, IL-5 and IFN-γ-mRNA tended to be decreased in the GK1.5 group. Conclusions Blocking/depleting of CD4+ cells inhibits the LPR in a mouse model of asthma. Thus, CD4+ lymphocytes might play a key role in the induction of the bronchial LPR.

Susceptibility to Cytomegalovirus Infection May Be Dependent on the Cytokine Response to the Virus

BackgroundCytomegalovirus (CMV) infection is an important cause of morbidity and mortality in an immunocompromised host. Pulmonary infection with CMV results in an inflammatory response, which includes the local production of...

Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases.

Complement receptor type 1 (CR1) (CD35; C3b/C4b receptor) is a transmembrane protein of many haematopoietic cells. Once cleaved, soluble complement receptor type 1 (sCR1) exerts opposite effects as a powerful inhibitor of complement. This study addressed both the question of whether sCR1 was found in bronchoalveolar lavage (BAL) of normals and patients with various inflammatory disease, and its possible origin. In this retrospective study covering specimen and clinical data of 124 patients with acute and chronic inflammatory lung pathologies, BAL supernatants were analysed by enzyme-linked immunosorbent assay technique for sCR1. Correlations were made between the sCR1 levels obtained and the constituents of BAL. Human alveolar macrophages were cultivated in order to determine their secretory capacity of sCR1. Alveolar macrophages from normal subjects were shown to release sCR1 in vitro. In addition, sCR1 was present in BAL of normal controls and was significantly increased in acute inflammatory lung diseases such as acute respiratory distress syndrome (ARDS), bacterial and Pneumocystis carinii pneumonia, as well as in chronic inflammatory diseases such as interstitial lung fibrosis and sarcoidosis. In BAL of ARDS, bacterial, and P. carinii pneumonia, there was a good correlation between sCR1 and the absolute neutrophil counts. In sarcoidosis, a correlation was found with BAL lymphocyte counts. Serum sCR1 was not increased in patients compared to controls. Soluble complement receptor type 1 (sCR1) is found in the bronchoalveolar lavage in health as well as in acute and chronic inflammatory disease. Alveolar macrophages are capable of releasing sCR1 in vitro and may be the main physiological source of sCR1 in the alveoli. The good correlation between sCR1 and the absolute neutrophil or lymphocyte numbers in bronchoalveolar lavage of inflammatory diseases suggests a predominant role of leucocytes for the release of sCR1 in such conditions. The release of this inhibitor of complement may be crucial to control and reduce complement activation and thus prevent lung injury.

Changes in bronchoalveolar lavage inflammatory cells in asthmatic patients treated with high dose inhaled beclomethasone dipropionate

Using serial bronchoalveolar lavage (BAL), we have studied changes in the airway inflammatory cell populations in 20 asthmatic patients, before and after treatment with inhaled beclomethasone dipropionate (BDP), 2,000 micrograms daily in an uncontrolled study. There was a significant improvement in asthma severity, as measured by symptom score and airways responsiveness, and there were significant reductions in the total BAL eosinophil, epithelial cell and mast cell counts, with a significant increase in the percentage BAL lymphocyte count. No significant correlations were found between the changes in airway inflammatory cell numbers and the reduction in asthma severity. In contrast, the fall in ROS generation by the pulmonary macrophage and granulocyte populations was nonsignificant, but the improvement in airways responsiveness was positively correlated to the reduction in the unstimulated pulmonary macrophage activity. Although these data are uncontrolled, the results are compatible with previous studies in suggesting an effect of steroids on the eosinophil, mast cell and epithelial cell in asthmatic airways. They also highlight the probable importance of the luminal lymphocyte population and pulmonary macrophage activation within the asthmatic airway, the beneficial modulatory effect of inhaled BDP treatment upon them, and the relative steroid-resistance of pulmonary inflammatory cell activity.

Prognostic Value of Bronchoalveolar Lavage Lymphocyte Count in Recently Diagnosed Pulmonary Sarcoidosis

We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment.

Lavage versus serum measurements of lysozyme, angiotensin converting enzyme and other inflammatory markers in pulmonary sarcoidosis

The aim of this study was to explore whether amounts of angiotensin converting enzyme (ACE) and lysozyme produced within the lungs correlate more closely than serum levels of these enzymes, or other inflammatory markers, with chest radiographic profusion scores, lung function and therapy response in patients with pulmonary sarcoidosis. We have studied 25 patients, and levels in bronchoalveolar lavage (BAL) were used to determine "local" enzyme production by reference to serum and lavage albumin. Before treatment, serum lysozyme levels were elevated in more patients (80%) than serum ACE levels (40%). They also gave the best overall correlation with clinical measurements prior to treatment and falls in serum lysozyme closely parallelled improvement in lung function (transfer factor for carbon monoxide (DLCO)) on therapy. The only other markers showing significant correlations with disease severity were lavage neutrophil counts per ml and "local" ACE measurements prior to treatment. The value of pre-treatment levels of the different inflammatory markers in predicting response to corticosteroid therapy was explored and the only significant finding was that BAL lymphocyte percentages and numbers.ml-1 were initially higher in patients with lower post-treatment chest X-ray scores (p less than 0.01 and p less than 0.05, respectively). We conclude that serum lysozyme levels appear to be a more useful marker of overall disease activity in sarcoidosis than measurements of other inflammatory markers. However, BAL lymphocyte counts were the best predictive marker of radiographic response to corticosteroids.

Lymphocyte subsets in bronchoalveolar lavage fluid obtained from stable asthmatics, and their correlations with bronchial responsiveness.

Bronchial responsiveness to methacholine (PD20 FEV1) was assessed in 22 asthmatic subjects approximately 5 days prior to bronchoalveolar lavage (BAL). A PD20 FEV1 could not be attained in 20 matched controls with normal pulmonary function. BAL was performed in all subjects, 3 x 60 ml aliquots of buffered saline being introduced into a segment of the middle lobe and immediately aspirated into siliconized glassware at 4 degrees C. After filtration, cells were counted, and the cell pellet resuspended in medium 199. Cytospin slides were prepared and a differential cell count performed. Lymphocyte subsets were identified by labelling further cytospin preparations with specific monoclonal antibodies (Leu series) against T3, T4, T8 and B cell markers, followed by a fluorescent antibody marker. The slides were coded, and 100 lymphocytes were then randomly scanned for fluorescence on each cytospin preparation. The median total lymphocyte counts were significantly greater in the asthmatic subjects, but this increase was confined to the T cell subgroups. The mean T4/T8 ratio was similar in asthmatic (1.51) and control (1.45) subjects. Log PD20 FEV1 correlated positively with total lymphocyte counts (r = 0.42, P less than 0.05), and with total T8 counts (r = 0.60, P less than 0.05). Correlations between bronchial responsiveness and T3, T4 and B lymphocyte numbers all failed to reach significance, and there was no correlation with T4/T8 ratios. The increase in BAL lymphocyte counts in asthma appears to be due to an absolute increase in T cell subsets, especially the T8 lymphocyte subgroup, and is most marked in mild asthmatics.

Serum C-reactive protein concentrations in patients with pulmonary sarcoidosis.

In a prospective study serum C-reactive protein concentrations were measured in nine patients with "active" pulmonary sarcoidosis (as assessed by bronchoalveolar lavage lymphocyte counts, gallium-67 lung scanning, and serial pulmonary function testing), and in five patients with "inactive" disease. Active pulmonary sarcoidosis was associated either with no rise or with only a modest rise in serum C-reactive protein concentrations. In contrast, serum C-reactive protein concentrations in 12 patients with sputum positive pulmonary tuberculosis were considerably raised. Serum C-reactive protein may thus provide a valuable test in the differentiation of sarcoidosis from conditions which it may mimic and which are known to induce an acute phase response.