Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects

Bronchoalveolar lavage (BAL) was performed on 28 asthma patients, 7 patients with emphysema and 11 control subjects. Total and differential cell counts were performed and cellular metabolic activity was assessed using luminol and lucigenin amplified chemiluminescence. BAL supernatants were assayed for platelet-activating factor (PAF) and lyso-PAF using a sensitive guinea-pig bioassay. Eight of the asthma patients but none of the emphysema patients or control subjects had PAF in their BAL fluid. Lyso-PAF was measurable in BAL fluid in most subjects and no differences were detected between groups. Among the asthma patients, the presence of PAF in BAL supernatant was significantly associated with a combination of low neutrophil and high lymphocyte counts (p less than 0.05) and with macrophage metabolic activity as assessed by lucigenin chemiluminescence (p less than 0.05).     

Differential cytology of bronchoalveolar lavage fluid in asthmatic children

Although asthma usually begins in childhood, limited information is available as to the inflammatory reaction of asthmatic children compared to adults and the influence of age. We investigated the cytology of bronchoalveolar lavage fluid (BALF) in 39 newly diagnosed wheezy children (minimum of 3 wheezing episodes during last 6 months): 21 allergic and 18 nonallergic subjects. None had received antiinflammatory treatment. Bronchoalveolar lavage (BAL) was performed, instilling 0.5 ml.kg(-1) body weight of warmed saline in 4 successive fractions. The first 2 aliquots (BALF 1) were pooled for microbiology and cytology, and the last 2 (BALF 2) for cytology only. Recovery correlated inversely with age, the most significant being for BALF 2 (r = -0.52, P = 0.001). Children under 2 years of age had larger amounts of ciliated columnar and goblet cells (P = 0.0074). Other cell types did not show age dependency. Differential cytology was characterized by a high number of creola bodies, bronchial epithelial cells (M = 68 x 10(3).ml(-1), R = 5-349), and neutrophils (M = 92 x 10(3).ml(-1), R = 0-1,257). Eosinophils were the only cells distinguishing allergic from nonallergic subjects (P = 0.003). The 16 children with positive microbiology had more neutrophils than the noninfected (P = 0.008), the latter still having more neutrophils than found in adults. These data suggest a limited age dependency in BALF cytology. Differential cytology in BALF might be helpful in differentiating asthma in children. Neutrophil inflammation might be more important than in adults.     

Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema.

Evidence for the contribution of neutrophils to the pathogenesis of pulmonary emphysema is not convincing. We evaluated neutrophil involvement in subclinical pulmonary emphysema by measuring human neutrophil lipocalin (HNL) and two matrix metalloproteinases, gelatinase B (MMP-9) and neutrophil collagenase (MMP-8), in bronchoalveolar lavage fluid (BALF) from 65 community-based older volunteers. HNL is a recently isolated 24-kD protein secreted from secondary granules of activated neutrophils. Despite no appreciable increase in the number of neutrophils, the level of HNL was significantly increased in BALF from subjects with emphysema evidenced by computed tomography regardless of current smoking, as compared with smokers without emphysema. The levels of MMP-9 and MMP-8 were also significantly higher in current smokers with emphysema than in those without emphysema. The appearance of a 130-kD HNL/MMP-9 complex on gelatin zymography and HNL immunoblot indicated neutrophils to be a significant source of MMP-9 in the subjects' BALF. In a 24-h culture medium of alveolar macrophages, only a latent form of MMP-9 was detected, and there was no difference in the level of MMP-9 between the groups. These data provide further evidence for neutrophil involvement in subclinical pulmonary emphysema.     

Cotinine levels in serum and bronchoalveolar lavage fluid

Cotinine is a major metabolite of nicotine. This study was planned to investigate the relationship between bronchoalveolar lavage (BAL) fluid cotinine levels and serum cotinine levels in smokers and nonsmokers with various pulmonary diseases and to investigate whether these levels are affected by passive smoking. Serum and BAL fluid cotinine levels were measured in 27 patients. BAL cotinine levels were measured using a sensitive ELISA kit produced to measure cotinine in saliva. Plates were read by microuant (BioTek, USA) micro plate reader. All patient serum cotinine levels were detectable except for one nonsmoker patient. However, BAL fluid cotinine levels were measurable in only 6 patients (two of them were nonsmokers). A significant positive correlation was seen between serum and BAL fluid cotinine levels (r = 0.726; p = 0.000). Serum cotinine levels were significantly higher in present smokers than non-smokers (21.0 +/- 16.01; 5.35 +/- 7.65; p = 0.004). However, there were no significant differences in BAL fluid cotinine levels between smokers and nonsmokers. Passive smoking can increase nicotine metabolites in serum and other body fluids, including BAL fluid. Since BAL fluid and serum cotinine levels were well correlated, there is no need to use invasive procedures, such as bronchoscopy and expensive, time consuming BAL fluid analyses. Serum cotinine levels can give a rough idea of smoking status. BAL fluid cotinine meaurements should be done for only scientific reasons.     

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.     

特发性肺纤维化患者支气管肺泡灌洗液和血清基质金属蛋白酶及其抑制剂检测

目的探讨特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)及血清中基质金属蛋白酶9(MMP9)、基质金属蛋白酶组织抑制剂1(TIMP1)水平的变化。方法2001至2004年用酶联免疫吸附(ELISA)法检测30例IPF患者BALF及血清中MMP9和TIMP1的水平,同时行肺高分辨率CT(HRCT)及肺功能检查。健康非吸烟的自愿献血者30名,为血清对照组。以胸痛为自觉症状在我院自愿进行纤维支气管镜及BALF检查,经体检及X线检查证实为健康者13名,作为BALF对照组。结果IPF患者BALF及血清中MMP9水平为(245±26)和(203±32)ng/L,对照组为(205±22)和(186±16)ng/L,两组相比差异无统计学意义;IPF组BALF及血清中TIMP1水平[(522±81)、(166±29)ng/L]高于对照组[(201±31)、(87±16)ng/L],差异有统计学意义;IPF组BALF及血清中MMP9/TIMP1比值(0.53±0.18,1.5±0.3)低于对照组(1.06±0.38,2.6±0.5)。HRCT、肺功能评分及BALF中上述指标与MMP9无明显相关性,与TIMP1呈正相关,与MMP9/TIMP1比值呈负相关。结论IPF患者肺纤维化的发生与TIMP1水平升高及MMP9/TIMP1比值降低对细胞外基质降解的抑制有关,后者可能意义更大;患者肺影像学及肺功能变化可能也与此有关。     

The concentration of leukocyte elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy human subjects

Although alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is widely thought to protect lung elastin against the elastolytic action of leukocyte elastase, there is only circumstantial evidence for such a protective role. We have demonstrated and quantified elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy smokers and nonsmokers using a new enzyme-linked immunosorbent assay. The relative concentration of complex is 0.36 +/- 0.48 mmol/mol albumin in nonsmokers and 0.33 +/- 0.29 mmol/mol albumin in smokers. Less than 1% of lavage fluid alpha 1-proteinase inhibitor is complexed with elastase (0.31% in nonsmokers and 0.34% in smokers). This proportion is, however, much higher than in normal plasma where only approximately 0.006% of inhibitor is bound to elastase. Our data confirm that alpha 1-proteinase inhibitor efficiently acts as an antielastase barrier in the lower respiratory tract.     

The origin of water and urea sampled at bronchoalveolar lavage in asthmatic and control subjects.

Bronchoalveolar lavage (BAL) urea has been advocated as a denominator that might allow for the dilution of the pulmonary epithelial lining fluid sampled at BAL, and so provide a meaningful method of expressing BAL data. We investigated the origin of water and urea sampled at BAL in five asthmatic and five control subjects using radiolabeled urea injected intravenously 5 min before BAL. Labeled BAL urea was found to be fully equilibrated with that in the bloodstream. A strong relationship was found between influx of radiolabeled water and radiolabeled urea from blood to BAL fluid, suggesting that urea sampled at BAL may be derived predominantly from an acute movement from the bloodstream into the BAL aspirate. We conclude that urea is an inappropriate denominator for the expression of BAL results, and that the fluid and solute dynamics that occur during BAL are both complex and variable.     

Bronchoalveolar lavage fluid from asthmatic subjects is mitogenic for human airway smooth muscle

Airway smooth muscle proliferation may contribute to the airway wall remodeling seen in asthma. In this study we tested for the presence of airway smooth muscle mitogenic activity in bronchoalveolar lavage (BAL) fluid obtained from 12 atopic asthmatics before and serially after segmental allergen challenge, and from four normal subjects who did not undergo allergen challenge. Mitogenic effect was assessed by coincubating BAL fluid with human airway smooth muscle cells, and measuring its effect on (3)[H]thymidine incorporation and cell number. Induction of ERK phosphorylation and cyclin D(1) protein abundance were also assessed. Compared with serum-free medium alone, BAL fluid obtained from normal subjects increased thymidine incorporation, cell number, ERK phosphorylation, and cyclin D(1) abundance. BAL fluid from asthmatic subjects prior to allergen challenge induced even greater increases in all measures, except for cell number, which was similar to that observed with normal subjects' BAL fluid. Incubation with lavage fluid obtained 48 h after segmental allergen challenge in atopic asthmatics caused yet further increases in thymidine incorporation, cell number, and cyclin D(1) protein abundance. Molecular sieving of prechallenge BAL fluid from three asthmatic subjects demonstrated that mitogenic activity was present exclusively in the > 10 kD fraction. These results provide the first direct demonstration that fluid lining the airways of asthmatics contains excess mitogenic activity for human airway smooth muscle, and that this activity increases further after allergen challenge.     

Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid.

Bacterial endotoxin has been suggested as responsible for the development of subjective symptoms and transient or chronic lung function impairment seen after exposure to organic dusts in cotton mills, poultry houses, swine confinement buildings and saw mills. Animal experiments have demonstrated bronchoalveolar neutrophilia being the most prominent cell response in animals following bacterial lipopolysaccharide (LPS) inhalation. The present study was conducted to obtain information on some aspects of the early inflammatory response to inhaled LPS in man. Eight healthy nonsmoking subjects, 23-27 yrs old, underwent bronchoalveolar lavage (BAL), 3 h after a provocation test with 100 micrograms LPS from E. coli dissolved in 2 ml isotonic NaCl. The solution was aerosolized with a jet nebulizer and inhaled. The calculated dose delivered to the lung was approximately 25 micrograms, which equals exposure in some occupational settings. The BAL data for each individual subject were compared with data from a control BAL performed at least 6 weeks prior to the LPS challenge. The major cellular response to LPS, reflected in BAL fluid, was an approximately hundredfold increase in neutrophils. The total number of lymphocytes was on average tripled. The alveolar macrophage phagocytosis of opsonized yeast particles in vitro was significantly reduced. A further indicator of an ongoing inflammation was an increase in fibronectin. No changes were seen in the levels of BAL albumin, indicating that the elevated level of fibronectin could not be explained by an increased permeability, but rather by a local production. The results correspond with data from animal studies and further supports the hypothesis that bacterial LPS is important in the pulmonary reaction induced by organic dusts.     

Acute effect of nitrogen dioxide exposure on the functional activity of alpha-1-protease inhibitor in bronchoalveolar lavage fluid of normal subjects

Nitrogen dioxide is one form of an oxidizing free radical that is sufficiently stable to exist in relatively high concentrations in ambient air and cigarette smoke. We examined the effect of NO2 exposure on the functional activity against pancreatic elastase of alpha-1-protease inhibitor (alpha 1PI) in bronchoalveolar lavage (BAL) fluid of nonsmoking subjects. Ten nonsmokers (mean age, 25 +/- 2 SE yr) were exposed to NO2 (3 or 4 ppm) for 3 h with intermittent exercise. Seven nonsmokers (mean age, 24 +/- 2 SE yr) underwent a similar protocol but were exposed to NO2-free air and served as control subjects. Bronchoalveolar lavage was performed 3.5 to 4 h after the end of exposure. Exposure to NO2 caused a 45% decrease in functional activity of alpha 1PI in BAL. There was no significant difference in immunoreactive alpha 1PI between the groups whether expressed as micrograms per 100 ml of recovered fluid or per milligram of albumin. This inactivation of alpha 1PI was not associated with any neutrophil migration into the air spaces of the lung. The "elastaselike" activity of BAL using synthetic elastinlike chromophore substrate succinyl-trialanine-nitroanilide showed no significant difference between the NO2-exposed group (221 +/- 39 SE ng/dl BAL) and the control group (196 +/- 61 SE ng/dl BAL). Assay for human leukocyte elastase (HLE) in concentrated BAL using the synthetic substrate Methoxysuc-Ala3-Pro-Val-aminomethylcoumarin did not detect any HLE activity in the BAL. These results showed that nonsmoking subjects exposed to relatively low concentrations of NO2 for a short time have a significant inactivation of alpha 1PI in the lower respiratory tract fluid than did nonsmoking control subjects.     

Fractional processing of sequential bronchoalveolar lavage fluid from intubated babies.

Two groups of intubated newborn babies were studied to determine the clinical effects of interrupted bronchoalveolar lavage (BAL) by suction catheter (S-BAL) and the similarities to adult fibreoptic BAL of fractional processing of sequential lavage fluid (BALF). Both groups were lavaged by two aliquots of 1 ml.kg-1, instilled via a blindly placed suction catheter, wedged on two separate insertions through the right main bronchus. In 14 infants, (sequential lavage group), BALF aliquots were analysed separately. There were no differences in the volumes recovered or total cell counts between the first and second BALF aliquots. Where cell morphology was visible (n = 11), the percentage of macrophages, but not the absolute number, increased in the second BALF aliquot (p less than 0.01). BALF urea and epithelial lining fluid volume estimated by urea dilution were similar between the two aliquots (n = 8). In a separate group (blood gas group), vital signs were recorded in 10 infants undergoing S-BAL. At 1 min after lavage there was a rise in mean arterial blood pressure (39 vs 49.5 mmHg, p less than 0.05) and a fall in transcutaneous oxygenation (10.6 vs 7.5 kPa, p less than 0.05). Recovery was present at 3 min post-S-BAL, but mean blood pressure remained elevated (39 vs 45 mmHg, p less than 0.05) and transcutaneous oxygen continued to be lower when compared to baseline values (10.6 vs 9.2 kPa, p less than 0.05). S-BAL of intubated infants appears to sample both the proximal and distal airways and results in changes in vital signs similar to routine non-selective endotracheal suctioning.     

特发性肺纤维化和结节病患者基质金属蛋白酶的变化及其临床意义

Objective To detect the levels of matrix metalloprotease(MMP)-1 and MMP-7 in the serum and the bronchoalveolar lavage fluid(BALF)of patients with idiopathic pulmonary fibrosis(IPF)and sarcoidosis(Stage Ⅱ),and therefore to investigate the significance of these changes in the pathogenesis of IPF. Methods Forty-four clinically confirmed cases of IPF were recruited,with the patients'age ranging from 46 to 70 years(58±9 years).Twenty patients with sarcoidosis,aged 35 to 65(50±12)years,were also studied.Enzyme-linked immunoabsorbent assay was used to detect the levels of MMP-1 and MMP-7 in the serum and the BALF samples. Results In the serum of patients with IPF,the level of MMP-1 [3.78 (0.14-13.44) μLg/L]was lower than that in patients with sarcoidosis[7.79(4.67-10.68)μg/L(z=-3.53,P<0.01)],but the level of MMP-7[7.83(3.57-14.37) μg/L]was higher than that in patients with sarcoidesis[4.04(0.06-9.94)μg/L(z=-3.84,P<0.01)].In the BALF of patients with IPF,the level of MMP-1 [1.09(0.04-5.14)μg/L]was lower than that in patients with sarcoidosis [2.08(0,05-4.16)μg/L(z=-1.53,P>0.05)],but the level of MMP-7[3.75(1.10-9.87)μg/L]was highet than that in patients with sarcoidosis[1.16(0.02-4.47)μg/L(x=-5.33,P<0.01)].The serum level of MMP-7 in patients with IPF was negatively correlated with the diffusing capacity of carbon monoxide(r=-0.56,P<0.01)and the percentage of neutrophils(r=-0.47,P<0.01).The level of MMP-7 in the BALF showed a negative correlation with diffusing capacity of carbon monoxide(r=-0.31,P <0. 05). Conclusions The results suggest that MMP-1 may be increased in the inflammatory phase as compared to the matrix remodeling phase of lung fibrosis, while MMP-7 may be increased in the matrix remodeling phase rather than in the inflammatory phase. MMP-7 may act as an important indicator for the severity of IPF.     

特发性肺纤维化和结节病患者基质金属蛋白酶的变化及其临床意义

目的 探讨特发性肺纤维化(IPF)和结节病患者基质金属蛋白酶(MMP)-1和MMP-7的变化及其临床意义. 方法 经临床确诊的IPF患者44例为IPF组,其中男23例、女21例,年龄46～70岁,平均(58±9)岁;Ⅱ期结节病患者20例为结节病组,其中男9例、女11例,年龄35～65岁,平均(50±12)岁.均进行肺功能和支气管肺泡灌洗检查.采用酶联免疫吸附试验测定血清和BALF中MMP-1和MMP-7水平.非正态分布的计量资料以中位数表示,采用两个独立样本比较的Wilcoxon秩和检验进行统计学分析,采用Spearson相关性检验进行相关分析. 结果 IPF组患者血清和BALF中MMP-1中位数(范围)分别为3.78(0.14～13.44)和1.09(0.04～5.14)μg/L,均明显低于结节病组的7.79(4.67μ10.68)和2.08(0.05μ4.16) μg/L,两组血清中MMP-1水平的差异有统计学意义(z=-3.53,P<0.01);IPF组患者血清和BALF中MMP-7中位数(范围)分别为7.83(3.57～14.37)和3.75(1.10～9.87)μg/L,均明显高于结节病组的4.04(0.06～9.94)和1.16(0.02～4.47)μg/L,两组血清和BALF中MMP-7水平的差异均有统计学意义(z值分别为-3.84和-5.33,均P<0.01).IPF组患者血清中MMP-7水平与DLCO占预计值%和BALF中性粒细胞构成比呈显著负相关(r值分别为-0.56和-0.47,均P<0.01),IPF组患者BALF中MMP-7水平与DLCO占预计值%呈显著负相关(r=-0.31,P<0.05). 结论 在肺纤维化炎症细胞浸润阶段MMP-1水平高于纤维化阶段,在纤维化基质重塑阶段MMP-7水平高于炎症阶段.MMP-7有可能作为肺纤维化严重程度的参考指标.     

Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease

The concentration and distribution of immunoglobulin isotypes (IgG, IgM, sIgA) and IgG-subclass levels (IgG-1-4) were measured in bronchoalveolar lavage fluid (BALF) in 47 children with chronic chest disease (age range 1.0-9.9 years) and 18 healthy controls (age range 1.0-6.25 years). Of these patients, 19 had nonallergic asthma (Group A), 19 suffered from recurrent pneumonia or chronic bronchitis (Group B), and 9 patients had IgG-2 deficiency (Group C). In all individuals, IgG was the predominant immunoglobulin in the lower respiratory tract, followed by IgA and IgM. In patients of Group A and B, IgG, IgM and IgA levels in BALF were significantly elevated when compared to controls. Assessment of IgG-subclass concentrations in BALF revealed that IgG-1 levels were increased in Group A and B when compared to controls (P < 0.05). Since this difference could not be explained by difference in age, it is possibly due to the inflammatory process at the mucosal level. IgG-2 levels were elevated in all patients except those with IgG-2 deficiency. IgG-2 concentration in the IgG-2 deficent group was lower compared to controls (P < 0.005) and patients in Group A (P < 0.0005) and B (P < 0.005). IgG-3 levels were elevated in asthmatics in group A compared to healthy controls (P < 0.005). IgG-4 concentrations were the same in all study groups. Since IgG-subclasses in percentage of total IgG were similar in BALF and serum, our results do not indicate a local production of any of the IgG-subclasses in the respiratory tract.     

Low neutral endopeptidase levels in bronchoalveolar lavage fluid of lung cancer patients

Neutral endopeptidase (NEP) is a cell surface enzyme found in normal human lung and which hydrolyzes small bioactive peptides, some of which act as growth factors for normal and malignant airway epithelial cells. Expression of NEP varies widely in human lung tissue from different individuals. NEP is often expressed at low or undetectable levels in both small-cell and non-small-cell lung cancer, and inhibits the growth of lung cancer cell lines. Variation in the expression of NEP could be a factor in susceptibility to lung cancer. We hypothesized that NEP could be measured in bronchoalveolar lavage fluid (BALF) and that airway levels of NEP would be low in lung cancer patients as compared with normal controls. We measured NEP and total protein in cell-free BALF supernatant, and expressed the respective concentrations as a ratio. NEP levels showed wide variation in BALF of healthy volunteers. Most patients with lung cancer had no NEP detectable in BALF. The mean NEP/total protein ratio was significantly lower in patients with lung cancer (0.87 +/- 0.7 ng NEP/mg protein) than in normal healthy subjects (14.0 +/- 4.3, p < 0.0003). We conclude that NEP levels are highly variable in BALF of normal volunteers, and are low or undetectable in most BALF specimens from patients with lung cancer. Low NEP levels in the airways may be a factor in the pathogenesis of carcinoma of the lung.     

特发性肺纤维化和结节病患者基质金属蛋白酶的变化及其临床意义

Objective To detect the levels of matrix metalloprotease(MMP)-1 and MMP-7 in the serum and the bronchoalveolar lavage fluid(BALF)of patients with idiopathic pulmonary fibrosis(IPF)and sarcoidosis(Stage Ⅱ),and therefore to investigate the significance of these changes in the pathogenesis of IPF. Methods Forty-four clinically confirmed cases of IPF were recruited,with the patients'age ranging from 46 to 70 years(58±9 years).Twenty patients with sarcoidosis,aged 35 to 65(50±12)years,were also studied.Enzyme-linked immunoabsorbent assay was used to detect the levels of MMP-1 and MMP-7 in the serum and the BALF samples. Results In the serum of patients with IPF,the level of MMP-1 [3.78 (0.14-13.44) μLg/L]was lower than that in patients with sarcoidosis[7.79(4.67-10.68)μg/L(z=-3.53,P<0.01)],but the level of MMP-7[7.83(3.57-14.37) μg/L]was higher than that in patients with sarcoidesis[4.04(0.06-9.94)μg/L(z=-3.84,P<0.01)].In the BALF of patients with IPF,the level of MMP-1 [1.09(0.04-5.14)μg/L]was lower than that in patients with sarcoidosis [2.08(0,05-4.16)μg/L(z=-1.53,P>0.05)],but the level of MMP-7[3.75(1.10-9.87)μg/L]was highet than that in patients with sarcoidosis[1.16(0.02-4.47)μg/L(x=-5.33,P<0.01)].The serum level of MMP-7 in patients with IPF was negatively correlated with the diffusing capacity of carbon monoxide(r=-0.56,P<0.01)and the percentage of neutrophils(r=-0.47,P<0.01).The level of MMP-7 in the BALF showed a negative correlation with diffusing capacity of carbon monoxide(r=-0.31,P <0. 05). Conclusions The results suggest that MMP-1 may be increased in the inflammatory phase as compared to the matrix remodeling phase of lung fibrosis, while MMP-7 may be increased in the matrix remodeling phase rather than in the inflammatory phase. MMP-7 may act as an important indicator for the severity of IPF.