Effect of histamine H1 receptor antagonists on antigen-induced increase of cough sensitivity in guinea pigs

Eosinophilic airway inflammation and increased cough sensitivity without bronchial hyperresponsiveness are the pathologic and physiologic features of bronchodilator-resistant non-productive cough-associated global atopic tendency, abbreviated herein as atopic cough. Histamine H₁ receptor antagonists are effective in relieving the cough in nearly 60% of patients with atopic cough. However, there is no direct evidence that histamine H₁ receptor antagonists can reduce cough hypersensitivity associated with eosinophilic airway inflammation. The purpose of the present study was to clarify this issue. The number of coughs caused by inhalation of increasing concentrations of capsaicin (10^− 8, 10^− 6 and 10^− 4 mol/L) was counted 24 h after the administration of an aerosolized antigen in actively sensitized conscious guinea pigs and then bronchoalveolar lavage (BAL) was performed. Azelastine (0.1 or 1 mg/kg) or terfenadine (0.2 or 2 mg/kg) was given intraperitoneally 60 min before capsaicin provocation 24 h after the antigen challenge in sensitized guinea pigs. In addition, azelastine (0.1 or 1 mg/kg) was administered 90 min before the capsaicin challenge in naïve guinea pigs. The cough response to capsaicin and the number of eosinophils in BAL fluid (BALF) were significantly increased after antigen challenge. Azelastine and terfenadine significantly reduced the increased cough response after antigen challenge, while azelastine had no effect in naïve animals. In conclusion, histamine H₁ receptor antagonists reduce antigen-induced increases in cough sensitivity in sensitized guinea pigs without direct inhibition of a common cough reflex pathway.     

Bronchial and Bronchoalveolar Inflammation in Single Early and Dual Responders after Allergen Inhalation Challenge

To characterize the cellular inflammation at the bronchial and bronchoalveolar levels, we evaluated 43 patients with asthma who were sensitized to house dust mites. On 2 consecutive days patients underwent methacholine challenge and allergen bronchial challenge. In addition, 6, 24, or 72 h after allergen challenge, fiberoptic bronchoscopy with bronchial lavage (BL) and bronchoalveolar lavage (BAL) was performed. Patients belonging to the 6-h, 24-h, or 72-h group were divided further into two subgroups: those with isolated early response to allergen (LAR⁻), and those with dual response to allergen (LAR⁺). The percentage of eosinophils and of epithelial cells in BAL fluid was significantly higher in LAR⁺ than in LAR⁻ patients in the 6-h group (p < 0.05, each comparison), but not 24 or 72 h after (p > 0.05, each comparison). Similarly, the proportion of BL eosinophils was also higher in LAR⁺ than in LAR⁻ patients, both in the 6-h and in the 24-h group (p < 0.05, each comparison). In addition, increased proportions of BL neutrophils were present in the LAR⁺ patients belonging to the 24-h group (p < 0.05). Comparing ``proximal' = BL vs ``distal' = BAL data, we found a significantly higher proportion of epithelial cells in BL compared with BAL, in both LAR⁻ and LAR⁺ subjects, either 6, or 24, or 72 h after challenge (p < 0.01, each comparison) and increased percentages of BL neutrophils and eosinophils in LAR⁺ patients (p < 0.05, each comparison), but not in LAR⁻ patients, in the 24-h group. The percentages of BL or BAL macrophages and lymphocytes did not differ significantly among the different patient groups. These data indicate that the development of LAR after allergen inhalation challenge is associated with an early recruitment of eosinophils and with epithelial desquamation in the airways. In addition, after allergen challenge epithelial desquamation is more pronounced in the proximal than in the distal airways, independently of the type of bronchial response. Accepted for publication: 7 January 1997     

支气管刷检嗜酸粒细胞计数在嗜酸粒细胞性支气管炎诊断中的价值

目的探讨支气管刷检嗜酸粒细胞（EOS）计数在嗜酸粒细胞性支气管炎（EB）诊断中的价值。方法选择32例EB患者（EB组）,18例咳嗽变异性哮喘患者（CVA组）,26例其它病因咳嗽患者（其它病因组）和13名健康人（健康对照组）,分别进行诱导痰、支气管刷检洗涤液和支气管肺泡灌洗液（BALF）中EOS的检测。结果EB及CVA组各标本中EOS的比例较其它病因及健康对照组明显增高（P〈0．001）;在EB及CVA组,支气管刷检洗涤液中EOS的比例显著高于诱导痰和BALF（P均〈0．叭）;支气管刷检EOS计数诊断EB的敏感性、特异性、阳性预测值和阴性预测值分别为100％、71．9％、66．7％和100％。结论经纤支镜支气管刷检EOS计数在EB的诊断中具有较重要的价值。     

Cell profile and elastase activity in diffuse panbronchiolitis investigated by bronchoalveolar and bronchial lavage.

To examine the mechanism of tissue damage which causes bronchiolectasis in diffuse panbronchiolitis (DPB), the cellular components, elastase and its main inhibitor, alpha 1-protease inhibitor (alpha 1-PI) were measured in bronchoalveolar and bronchial lavage fluid (BALF and BLF) from 14 DPB patients. A predominant increase in the neutrophil count was observed in DPB. Elastase activity in BALF and BLF was about 1,000-fold higher in the DPB group than in the control group. An inhibitor study and a positive correlation between elastase activity and the neutrophil count in both lavage fluids from the DPB group indicated that the activity was mainly that of neutrophil elastase. Western blot analysis of alpha 1-PI showed that most of the alpha 1-PI in the lavage fluids from DPB group was degraded. These results indicated that neutrophil infiltration increases the level of elastase in the DPB lesions; this increase seems to be closely related to tissue damage.     

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.     

Chronic eosinophilic pneumonia associated with Schizophyllum commune

We describe the first known Japanese patient with chronic eosinophilic pneumonia caused by Schizophyllum commune. The patient presented to Social Insurance Tagawa Hospital, Fukuoka, Japan with cough, wheezing, dyspnoea, and fever. Computed tomograms of the chest showed bilateral areas of consolidation with air bronchograms as well as interstitial infiltrates in the upper lobe, without ectasia of proximal bronchi. Fibreoptic bronchoscopy revealed no impacted mucus in the bronchi. BAL fluid from the right upper lobe yielded an increased total cell count with a high percentage of eosinophils. A transbronchial lung biopsy specimen showed a bronchoalveolar chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells, associated with fibrosis of the alveolar walls. S. commune was identified in lavage fluid. Antibodies to this organism were present in the serum, confirming that S. commune was the cause of chronic eosinophilic pneumonia. Inhaled corticosteroids without accompanying oral corticosteroids or antifungal agents decreased the respiratory symptoms, and the infiltrates disappeared from the chest radiograph within a few days     

What are the factors affecting the recovery rate of bronchoalveolar lavage fluid?

BackgroundBronchoalveolar lavage (BAL) is a useful examination for the evaluation of interstitial lung disease. A high BAL fluid (BALF) recovery rate is desirable because low recovery rates lead to inaccurate diagnoses and increased adverse events. Few studies have explored whether BALF recovery rates are influenced by clinical factors.ObjectivesThis study aimed to identify the clinical parameters affecting the recovery rates of BALF and the extent of their effects.MethodData from patients who underwent BAL at the Chiba University Hospital between 2013 and 2019 were retrospectively reviewed. BAL was performed with three aliquots of 50‐ml physiological saline. The potential association of the BALF recovery rate with clinical parameters such as age, sex, smoking status, underlying disease, bronchus used for the procedure and pulmonary function, was analysed.ResultsEight hundred twenty‐six patients had undergone BAL. The average recovery rate was 52.4%. Factors affecting BALF recovery rates included male sex (odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.20–0.53, p < 0.001); age ≥ 65 years (OR: 0.50, 95% CI: 0.33–0.76, p < 0.001); use of the left bronchus (OR: 0.46, 95% CI: 0.30–0.71, p = 0.001) and bronchi other than the middle lobe bronchus or lingula (OR: 0.41, 95% CI: 0.25–0.65, p < 0.001); and forced expiratory volume in 1 s divided by forced vital capacity <80% (OR: 0.42, 95% CI: 0.40–1.00, p < 0.001).ConclusionSex, age, bronchus used for the procedure and pulmonary function may be useful as pre‐procedural predictors of BALF recovery rates.     

Airway inflammation and occurrence of delayed bronchoconstriction in exercise-induced asthma.

We studied nine asthmatic patients with a history of exercise-induced asthma (EIA) in order to investigate whether inflammatory changes in the airways occur after exercise and are eventually associated with the development of a late-phase asthmatic response. On two separate study days, bronchoalveolar lavage (BAL), bronchial lavage (BL), and bronchial biopsy (BB) were performed 3 h after an exercise or a methacholine (MCh) challenge. On two other separate occasions, FEV1 was monitored for 12 h after identical exercise and MCh challenges not followed by BAL, BL, and BB. We found a greater percentage of eosinophils in BAL after exercise versus MCh challenge (p < 0.05). In five patients, BAL eosinophils after exercise were > or = 2% of total inflammatory and immunoeffector cells. In three of these patients an FEV1 fall > 20% of control was recorded 5 to 12 h after exercise. However, two of these patients had 2% or more eosinophils in BAL and similar late falls of FEV1 after MCh challenge. The percentage of degranulating mast cells in BB was higher (p < 0.05) after EIA than after MCh, but no significant differences were found in BL histamine and leukotrienes. We conclude that (1) exercise may enhance mast cell degranulation and eosinophilic inflammation of the airways, and (2) a delayed bronchoconstriction after exercise is not specific to EIA but is more likely the result of fluctuations in lung function associated with airway inflammation.     

Bronchoalveolar lavage findings in patients with chronic nonproductive cough.

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.     

Elevated histamine content of lung lavage in human asbestosis

Increased histamine levels in lung lavage have been previously reported in humans with idiopathic fibrosing alveolitis and mast cell proliferation was documented on lung tissue. Similarly, mast cell proliferation has been documented in experimental asbestosis. To evaluate the relevance of these observations to human asbestosis, we performed bronchoalveolar lavage in 10 normal volunteers (group N) and 22 long-term asbestos workers from the mines and mills of Quebec. The 22 asbestos workers were evaluated by standard clinical, functional, radiographic, and gallium-67 lung uptake tests. Five did not have any abnormality suggestive of asbestosis and constituted group A. The 6 in group B were without sufficient criteria for well-established asbestosis, but their lung pressure-volume curve was rigid and⁶⁷Ga lung uptake was increased; the 11 in group C had well-established asbestosis. In addition to standard parameters of BAL cellularity and biochemistry, we measured histamine levels by fluorometric method. In normals, histamine levels were 1.0 ± 0.3 ng/ml, in group A 1.25 ± 0.37 ng/ml (NS), in group B 2.26 ± 0.86 ng/ml (P < 0.05 B vs A or N), and in group C it was 2.65 ± 0.44 ng/ml (P < 0.05 C vs A or N). BAL eosinophils were absent in normals and group A, 272 ± 136/ml in group B, and 764 ± 350 in group C (P < 0.05 for groups B and C vs normals and group A), but did not correlate with histamine content of BAL. This study provides evidence of an elevated content of histamine in the bronchoalveolar milieu of patients with early and late asbestosis. This finding is of interest in relation to the potential role of the mast cell in the disease process.     

嗜酸粒细胞性支气管炎患者气道炎症细胞及介质特征的探讨

目的观察嗜酸粒细胞性支气管炎(EB)诱导痰和支气管肺泡灌洗液(BALF)中细胞分类和炎症介质浓度,探讨EB的气道炎症特征。方法对43例EB(EB组)患者行诱导痰检查,将20例咳嗽变异型哮喘(CVA)患者(CVA组)、16例典型支气管哮喘(哮喘组)患者和21名健康人(健康对照组)行对照诱导痰检查,并对部分EB(11例)和CVA患者(10例)行支气管肺泡灌洗(BAL)。观察检测诱导痰、BALF中的细胞分类、嗜酸粒细胞阳离子蛋白(ECP)、白三烯C4(LTC4)和组胺的浓度。结果EB组患者诱导痰中嗜酸粒细胞(EOS)百分比为0.1130±0.1470,CVA组为0.1900±0.1800,哮喘组为0.3860±0.2670,与健康对照组(0.0020±0.0050)比较差异有统计学意义(P均<0.01);哮喘组与CVA组、CVA组与EB组比较差异均有统计学意义(P均<0.05);EB组BALF中EOS为0.011±0.016,CVA组为0.053±0.040,两组比较差异有统计学意义(P<0.05);EB组诱导痰中的ECP浓度为(0.62±0.66)mg/L、CVA组为(1.27±1.74)mg/L,对照组为(0.07±0.10)mg/L,3组间比较差异有统计学意义(P<0.01);CVA组诱导痰中的LTC4浓度为(0.65±0.62)μg/L,EB组为(0.39±0.61)μg/L,对照组为(0.15±0.11)μg/L,3组间比较差异有统计学意义(P分别<0.05、0.01);CVA组BALF中组胺浓度为(3.4±1.4)μg/L,EB组为(1.6±1.5)μg/L,两组比较差异有统计学意义(P<0.05)。结论EB组EOS炎症主要局限于中心气道,部分气道炎性介质水平低于CVA组。上述气道炎性特征可能是EB患者无非特异性气道高反应性的重要机制。     

Detection of sputum Aspergillus galactomannan for diagnosis of invasive pulmonary aspergillosis in haematological patients

We investigated the diagnostic utility of Aspergillus galactomannan (GM) in sputum for diagnosis of invasive pulmonary aspergillosis (IPA) in haematologic patients and compared the results with those of bronchial lavage fluid (BLF) and serum. Patients were classified into 4 groups using modified European Organization for Research and Treatment of Cancer criteria: group A, proven IPA; group B, probable IPA; group C, possible IPA; group D, others. Groups A and B were considered the IPA group (n = 6); group D was considered non-IPA group (n = 37); group C (n = 13) was equivocal for IPA. As a true negative control, sputa from patients with community-acquired pneumonia (CAP) without risk factors (group E, n = 22) were used. From the receiver-operating characteristic curves, the cut-off levels were determined as 1.2 in sputum, 0.5–1.3 in BLF and 0.5 in serum. The sensitivity and specificity of sputum, BLF and serum GM were 100 and 62.2%, 66.7 and 100%, and 83.3 and 81.1%, respectively. Twenty-two patients with CAP (group E) showed median GM levels in the sputa of 0.1 (range 0.0–1.0). Sputum GM is a useful non-invasive test for screening of IPA in haematological patients, and may also be useful for assessment of the risk of developing IPA.     

Ultrastructural observation of eosinophils in bronchoalveolar lavage fluid in eosinophilic pneumonia]

To investigate the morphological changes of local eosinophils in the lungs, we observed the ultrastructure of eosinophils in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. We also measured the BALF concentration of eosinophil cationic protein (ECP) as an index of the activation of eosinophils. The eosinophils in BALF from patients with eosinophilic pneumonia showed various ultrastructural changes compared to eosinophils in BALF of the control patient. Changes included degranulation or disintegration of specific granules, cytoplasmic vacuolation, increased lipid droplets and the appearance of Charcot-Leiden crystals. These changes of BALF eosinophils were more prominent than those of peripheral blood eosinophils. ECP concentration (mean +/- SD) in BALF from patients with eosinophilic pneumonia was 12.2 +/- 7.78 micrograms/l which was significantly higher than the concentrations in patients with bronchial asthma not during an attack (1.36 +/- 2.08 micrograms/l) and in healthy control subjects (2.14 +/- 4.62 micrograms/l). These results suggest that local eosinophils in the lungs are activated and degranulated by various stimuli and undergo structural degeneration in eosinophilic pneumonia.     

Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndrome

Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N = 40) and another of non-asthmatic controls (N = 42), matched for age and sex. Prevalence of sensitization (>or=1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management.     

碱性成纤维细胞生长因子、纤维连接蛋白在肺炎支原体感染中的临床意义

目的探讨碱性成纤维细胞生长因子(bFGF)、纤维连接蛋白(FN)在肺炎支原体感染患者中的临床意义。方法对我院2007年1月～2009年6月108例慢性咳嗽患者行支气管肺泡灌洗液(BALF)肺炎支原体-聚合酶链反应(PCR)检测。根据检测结果,分为实验组72例(肺炎支原体阳性)与对照组36例(肺炎支原体阴性)。对两组患者进行支气管镜肺活检,通过酶联免疫吸附试验(ELISA)方法检测bFGF水平,Western blot方法检测FN水平。结果肺炎支原体感染组bFGF及FN水平明显高于对照组,差异有统计学意义(P0.05)。结论肺炎支原体肺部感染可使肺组织bFGF水平增加,而bFGF可进一步诱导FN表达增加。bFGF、FN检测对肺炎支原体所致肺间质纤维化患者早期诊断、病情动态变化、治疗有一定的参考价值。     

TRPC1对慢性阻塞性肺疾病慢性气道炎症的影响

目的探讨瞬时感受器电位通道C1(TRPC1)在慢性阻塞性肺疾病(慢阻肺)患者支气管黏膜上皮的表达水平及其与慢性气道炎症之间的关系。方法选取因不明原因肺部结节行纤维支气管镜检查的78例患者,依据慢性阻塞性肺疾病诊治指南分为慢阻肺组(46例)及对照组(32例),其中慢阻肺组再随机分为两个亚组:每日3次规律使用吸入型激素(ICS)布地奈德(ICS组,23例)及安慰剂(非ICS组,23例)治疗。所有受检查者均行支气管肺泡灌洗及支气管镜下刷检。Western Blot及qRT-PCR法检测刷检支气管上皮细胞内TRPC1表达水平,支气管肺泡灌洗液(BALF)行细胞学分类计数。酶联免疫吸附法检测BALF上清液中炎症介质白细胞介素13(IL-13)、成纤维生长因子2(FGF-2)表达水平。结果慢阻肺组支气管上皮细胞内的TRPC1 mRNA、蛋白表达水平明显高于对照组(P<0.05);ICS组的TRPC1表达水平低于非ICS组(P<0.05)。与对照组相比,慢阻肺组BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平均明显升高(P<0.05)。而ICS组BALF中的中性粒细胞、巨噬细胞、嗜酸性粒细胞、淋巴细胞计数及IL-13、FGF-2表达水平则低于非ICS组(P<0.05)。相关性分析结果显示,TRPC1 mRNA和蛋白表达水平与肺功能第一秒用力呼吸容积(FEV 1)占预计值百分比(FEV 1/Pre%)呈负相关(P<0.01),而与BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平呈正相关(P<0.05)。结论TRPC1可能通过参与慢阻肺慢性气道炎症过程促进疾病的发生发展,而ICS在一定程度上可干预该作用。     

High fever after flexible bronchoscopy and bronchoalveolar lavage in noncritically ill immunocompetent children.

Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have been applied increasingly to the evaluation of pulmonary disease in children. Although several complications have been reported following FB and BAL, high fever after BAL in immunocompetent children has not previously been reported. To determine the frequency, clinical characteristics, and outcome of these complications in children who developed high fever post-BAL, we retrospectively reviewed all bronchoscopic procedures done on an outpatient basis between August 1995 and July 1997. We identified 78 immunocompetent noncritically ill children who had undergone FB and BAL as an outpatient procedure for evaluation of underlying pulmonary disease, of whom 13 (17%) developed temperature (T) higher than or equal to 39 degrees C (fever group). The 13 patients in the fever group had a median age of 10 (range, 4-48) months and a reported T of 39.4 degrees C (39.1-40.6 degrees C) occurring 7.5 (4-12) hr after BAL. To determine if there were differences in clinical or BAL fluid (BALF) characteristics, we compared each child in the fever group to two children in the nonfever group, based upon primary indications and age. There were no differences in demographic or clinical characteristics between the two groups. Lymphocyte concentrations in BALF were significantly reduced in the fever group (P = 0.03). An abnormal BALF cell differential (defined as one or more of the following: neutrophils >10%, lymphocytes >30%, or eosinophils >1%) was significantly more common in the fever group (P = 0.008, odds ratio 3.6). We conclude that high fever is a frequent adverse event following BAL in noncritically ill immunocompetent children with underlying pulmonary disease. Pre-BAL clinical characteristics are not associated with development of high fever. However, the finding of an abnormal BALF cell differential is strongly associated with development of high fever post-BAL.     

The use of corticosteroids does not influence CD4+ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency

ABSTRACT

Corticosteroids inhibit HIV-related immune activation and seem to have a mild favorable effect on immunological recovery in patients with CD4⁺ counts ≥200?cells/mm³. Data in patients with advanced immunodeficiency are lacking. We analyzed whether corticosteroids negatively influence the short-term CD4⁺ lymphocyte recovery in patients with CD4⁺ cell counts <200?cells/mm³ started on combination antiretroviral therapy (cART). We performed a retrospective cohort analysis including all HIV-infected patients under follow-up in our hospital with a documented episode of Pneumocystis Jirovecii Pneumonia (PJP) in the cART era. CD4⁺ lymphocyte recovery was assessed at three months after the episode of PJP and subsequent start of cART, comparing patients that received adjunctive corticosteroids (AC) versus patients that did not receive corticosteroids (standard care (SC)). In total, 66 patients with an episode of PJP were identified with 38 patients in the AC-group versus 28 patients in the SC-group. Almost all baseline characteristics were similar, including mean CD4⁺ lymphocyte counts. After three months, the mean CD4⁺ cell count did not differ; 222?cells/mm³ for the SC-group versus 259?cells/mm³ for the AC-group (p?=?.29). The use of corticosteroids does not alter CD4⁺ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency in the first months of antiretroviral therapy.     

5-Aminosalicylic Acid Modulates the Immune Response in Chronic Beryllium Disease Subjects

Introduction

Chronic beryllium disease (CBD) is characterized by accumulation of macrophages and beryllium-specific CD4⁺ T cells that proliferate and produce Th1 cytokines. 5-Amino salicylic acid (5-ASA) is currently used to treat inflammatory bowel disease and has both antioxidant and anti-inflammatory actions. We hypothesized that 5-ASA may be a beneficial therapeutic in CBD.

Methods

Seventeen CBD patients were randomized 3:1 to receive 5-ASA 500-mg capsules or placebo four times daily for 6 weeks orally. Primary study endpoints included changes in beryllium lymphocyte proliferation (BeLPT). Secondary endpoints included changes in bronchoalveolar lavage (BAL) fluid, cells, serum, and blood cell glutathione (GSH) levels, BAL cell TNF-α levels, lung function, and quality of life measures.

Results

5-ASA decreased BAL cell BeLPT by 20% within the 5-ASA treatment group. No significant changes were observed in serum, PBMCs, BALF, or BAL cell GSH levels in either the 5-ASA or placebo treatment group. 5-ASA treatment decreased ex vivo Be-stimulated BAL cell TNF-α levels within the 5-ASA group and when compared to placebo. Significant improvements were noted in quality of life measurements with 5-ASA treatment.

Conclusions

5-ASA’s ability to decrease BAL cell BeLPT and Be-stimulated BAL cell TNF-α levels suggests that 5-ASA may impact the beryllium-specific immune response in CBD. 5-ASA use in other non-infectious granulomatous lung diseases, such as sarcoidosis, may prove to be a useful alternative treatment to corticosteroids for those with mild to moderate disease.