Is Metalloproteinase-7 Specific for Idiopathic Pulmonary Fibrosis?

BACKGROUND: Matrix metalloproteinase (MMP)-7 was reported to be a key molecule in the pathogenesis of idiopathic pulmonary fibrosis (IPF) based on the result of microarray analysis and knockout mice. However, the role of MMP-7 has not been determined in other types of idiopathic interstitial pneumonia (IIP). The aim of this study was to investigate the role of MMP-7 in IIP by comparing its expression in usual interstitial pneumonia (UIP) and cryptogenic organizing pneumonia (COP). METHODS: Levels of MMP and tissue inhibitors of metalloproteinase in BAL fluid and their expression on lung tissues were compared between normal control subjects (n = 5) and the patients with IPF (n = 6) and COP (n = 11). RESULTS: There was no significant difference in BAL fluid MMP-7 levels between UIP and COP, although it was higher in both diseases compared to normal control subjects. Furthermore, the pattern and the degree of MMP-7 expression in lung tissues were also similar in both IPF and COP, whereas MMP-2 level was higher in COP and MMP-9 level was higher in IPF. CONCLUSION: MMP-7 seems to play an important role in the pathogenesis of not only IPF but also COP; therefore, it may not be the key factor determining the prognosis or reversibility of IIPs.     

Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease

STUDY OBJECTIVES: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia. DESIGN: Retrospective review. SETTING: Two thousand-bed, university-affiliated, tertiary referral center. PATIENTS: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD. METHOD: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared. RESULTS: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively. CONCLUSIONS: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.     

Outcomes and safety of surgical lung biopsy for interstitial lung disease

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.     

Reducing the toll of inflammatory lung disease

Toll-like receptors (TLRs) are pivotal in human response to microbial stimuli. Their activation and signaling underpin much of the observed epidemiologic data generated by the hygiene hypothesis, and their contribution to infectious exacerbations of airways disease is likely to be highly important. Our growing knowledge in this field will have a significant impact on the understanding of the pathogenesis of inflammatory diseases, and TLR-based therapies are already in early clinical trials to modify atopic disease severity.