Histological Pattern Of Usual Interstitial Pneumonia Research Articles

Non-specific and Usual Interstitial Pneumonia, Short-Term Survival After Surgical Biopsy

To the Editors, Idiopathic interstitial pneumonia (IIP) is a diagnostic challenge. The diagnostic work-up in general includes medical history, physical examination, lung function tests, chest X-ray, high-resolution computed tomography and bronchoalveolar lavage. If no clinical diagnosis can be established on the basis of these data, a surgical lung biopsy might be indicated. In this setting, possible therapeutic and prognostic implications should be weighed against the risk of postoperative complications such as infections, prolonged air leakage, respiratory failure, acute exacerbation of underlying disease and even mortality. Review of literature shows that postoperative mortality after surgical lung biopsy in IIP was found to be 4.8 % after 30 days and 6 % after 90 days [1]. Reported risk factors for mortality were low diffusing capacity for carbon monoxide (DLCO) and low forced vital capacity (FVC) [2, 3]. There are reports suggesting that surgical lung biopsy itself increases the risk of acute exacerbation of underlying disease [2, 3]. The aim of this study was to evaluate the 30- and 90-day mortality rate after surgical lung biopsy in two histological distinct groups of patients: one with a histological pattern of usual interstitial pneumonia (UIP) and one with a pattern of non-specific pneumonia (NSIP). In this retrospective study, we included all patients with a histological UIP or NSIP who underwent surgical lung biopsy between 1993 and 2011 in our centre. Baseline characteristics are presented in Table 1. Data on mortality rate at 30 and 90 days, length of postoperative hospital stay, duration of air leakage, time to drain removal after surgery and infectious complications were collected. Table 1 Baseline characteristics Data of 69 patients were analysed (Table 1). There were 23 patients with histological NSIP and 46 with UIP. Baseline characteristics showed significant differences between both groups: mean forced expiratory volume in 1 s (FEV1) and diffusion capacity (DLCO) were lower in the NSIP group compared with the UIP group. Patients with a UIP pattern in this study were more often male and were older. No significant differences were found in FVC, total lung capacity, Body Mass Index (BMI) and smoking status. Overall, the 90-day mortality rate after surgical lung biopsy in all patients was 11.6 % (8 out of 69). In the UIP group, all patients who died underwent an open lung biopsy, the 30-day mortality rate was 8.7 % (4 out of 46) and the 90-day mortality rate was 15.2 % (7 out of 46). The median pre-operative FVC was 86 % and DLCO 46 % of the seven patients who passed away. Two patients died of pneumonia with radiologic evidence of progression of fibrosis. Post-mortem examination revealed diffuse alveolar damage in one case. Three patients died in the second and third month due to progression of fibrosis, and in two cases, this was proven by post-mortem examination and in one case radiologically. One cause of death was unknown due to loss to follow-up. Among seven patients with UIP who died, five were ultimately diagnosed to have idiopathic pulmonary fibrosis (IPF) and two to nonclassifiable interstitial pneumonia. In the NSIP group, only one patient died due to pneumonia in the first month after surgery. The 30- and 90-day mortality rates were both 4.3 % in the NSIP group. No significant differences were found in postoperative hospital stay (p = 0.906), duration of air leakage (p = 0.721), time to drain removal after surgery (p = 0.65) and infectious complications (p = 0.977) between the NSIP and UIP group. There was no correlation between year of surgery and mortality. Although the difference in mortality rate between the UIP and NSIP group was not statistically significant, we observed a trend towards a higher mortality rate in patients with UIP pattern, which is in agreement with reports in the literature [2, 3]. Interestingly, all deceased UIP patients with a known cause of death showed progression of fibrosis, while no progression of fibrosis was observed in the patient who died in the NSIP group. This observation suggests that the UIP non-survivors, who had relatively good pre-operative lung functions compared to the all NSIP patients, experienced rapid progression of their disease which cannot be excluded to be related to the surgical procedure. We hypothesize that this rapid progression of fibrosis might be induced by the surgical procedure itself causing increased damage of the highly vulnerable alveolar epithelium. Increased vulnerability of the alveolar wall appears to be a fundamental problem in IPF. In conclusion, mortality after surgical lung biopsy is relatively high, especially in patients with a histological pattern of UIP. We think that these results should be taken into account when considering open lung biopsy in patients with suspected IIP.

Fibrosis pulmonar idiopática

Idiopathic pulmonary fibrosis (IPF) is a chronic idiopathic disease differentiated, progressive fibrosing interstitial pneumonia. It usually affects adults over 50 years old and presents with progressive exertional dyspnea and dry cough. Prevalence rales were heard at bases in 90 % of patients and there clubbing in 50 %. Definitive diagnosis requires: a) the exclusion of other clinical entities defined or diffuse lung diseases of known cause; b) radiological evidence of a typical pattern of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT), the presence of a histological pattern of UIP on lung biopsy specimens adequate or both. The diagnostic accuracy improves with multidisciplinary assessment among clinicians, radiologists and pathologists expert. A better understanding of the pathogenesis of IPF has helped to launch several clinical trials in search of more selective and effective to the poor prognosis of the disease therapeutic strategies.

De la exclusión a la certidumbre. El recorrido hacia el diagnóstico de la fibrosis pulmonar idiopática

Idiopathic pulmonary fibrosis (IPF) is a differentiated disease within the idiophatic interstitial pneumonias. IPF is progressive and fibrosing and is limited to the lungs. This entity generally affects persons older than 50 years old and is associated with the radiological and/or histological pattern of usual interstitial pneumonia (UIP). Clinically, IPF causes progressive exertional dyspnea and nonproductive cough. In most patients, physical examination reveals fine bibasilar inspiratory crackles and 50% of patients have digital clubbing. There are no specific laboratory alterations. Bronchoalveolar lavage and transbronchial biopsy will not establish the diagnosis of IPF but are useful to exclude other entities. Definitive diagnosis requires: a) exclusion of other, defined clinical entities or diffuse pulmonary diseases of known cause, and b) the presence of a histological pattern of UIP on analysis of pulmonary tissue from surgical biopsy, radiological evidence of the defined pattern of UIP on high-resolution computed tomography, or both.

Interstitial and Vascular Type V Collagen Morphologic Disorganization in Usual Interstitial Pneumonia

Recent evidence suggests that type V collagen plays a role in organizing collagen fibrils, thus maintaining fibril size and spatial organization uniform. In this study we sought to characterize the importance of type V collagen morphological disorganization and to study the relationship between type V collagen, active remodeling of the pulmonary vascular/parenchyma (fibroblastic foci), and other collagen types in usual interstitial pneumonia (UIP). We examined type V collagen and several other collagens in 24 open lung biopsies with histological pattern of UIP from patients with idiopathic pulmonary fibrosis (IPF). We used immunofluorescence, morphometry, and three-dimensional reconstruction to evaluate the amount of collagen V and its interaction with the active remodeling progression in UIP, as well as types I and III collagen fibers. Active remodeling progression was significantly related to type V collagen density (p<0.05), showing a gradual and direct increase to minimal, moderate, and severe fibrosis degree in UIP and in the three different areas: normal, intervening, and mural-organizing fibrosis in UIP. Parenchymal changes were characterized by morphological disorganization of fibrillar collagen with diverse disarray and thickness when observed by three-dimensional reconstruction. We concluded that in the different temporal stages of UIP, vascular/parenchyma collagen type V is increased, in disarray, and is the most important predictor of survival.

Pulmonary pathology in association with connective tissue disorders

Patients with connective tissue disorders (CTD) often have associated pleuropulmonary lesions, and these are major causes of morbidity and mortality. CTD may involve all compartments of the respiratory system, including respiratory muscles, pleura and lung parenchyma, with diffuse interstitial pneumonia and fibrosis being common within the parenchyma. During the last decade, non-specific interstitial pneumonia (NSIP) has been recognized as a specific histological pattern, and the definition of usual interstitial pneumonia (UIP) has been narrowed and refined, this having significant impact on the diagnosis of interstitial pneumonias in CTD. Recent data suggest that a pattern of NSIP is the most common pattern of interstitial pneumonia in CTD such as scleroderma, dermatomyositis/polymyositis, rheumatoid arthritis, and Sjoegren's syndrome. This is consistent with the more favourable prognosis seen with interstitial pneumonias associated with CTD, in comparison to patients with idiopathic pulmonary fibrosis who, with rare exceptions, have a histological pattern of UIP.

Histopathologic variability in usual and nonspecific interstitial pneumonias.

Findings of surgical lung biopsy (SLB) are important in categorizing patients with idiopathic interstitial pneumonia (IIP). We investigated whether histologic variability would be evident in SLB specimens from multiple lobes in patients with IIP. SLBs from 168 patients, 109 of whom had multiple lobes biopsied, were reviewed by three pathologists. A diagnosis was assigned to each lobe. A different diagnosis was found between lobes in 26% of the patients. Patients with usual interstitial pneumonia (UIP) in all lobes were categorized as concordant for UIP (n = 51) and those with UIP in at least one lobe were categorized as discordant for UIP (n = 28). Patients with nonspecific interstitial pneumonia (NSIP) in all lobes were categorized as having fibrotic (n = 25) or cellular NSIP (n = 5). No consistent distribution of lobar histology was noted. Patients concordant for UIP were older (63 +/- 9 [mean +/- SD] yr; p < 0.05 as compared with all other groups) than those discordant for UIP (57 +/- 12 yr) or with fibrotic NSIP (56 +/- 11 yr) or cellular NSIP (50 +/- 9 yr). Semiquantitative high-resolution computed tomography demonstrated a varied profusion of fibrosis (p < 0.05 for all group comparisons), with more fibrosis in concordant UIP (2.13 +/- 0.62) than in discordant UIP (1.42 +/- 0.73), fibrotic NSIP (0.83 +/- 0.58), or cellular NSIP (0.44 +/- 0.42). Survival was better for patients with NSIP than for those in both UIP groups (p < 0.001), although survival in the two UIP groups was comparable (p = 0.16). Lobar histologic variability is frequent in patients with IIP, patients with a histologic pattern of UIP in any lobe should be classified as having UIP.