Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation.MethodsRetrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings.ResultsOut of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage.ConclusionsLung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

A Systematic Review of the Prognostic Significance of the Body Mass Index in Idiopathic Pulmonary Fibrosis

“…Among them, 1220 were excluded because they were either duplicates or irrelevant. After a full-text review of the remaining 37 articles, one was further excluded because it did not fulfill the inclusion criteria, thus leaving 36 studies (9958 IPF patients, 78% males) for final analysis [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] ( Figure 1 ). Fourteen studies were conducted in Japan [ 22 , 27 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 43 , 45 , 50 , 51 ], nine in the USA [ 21 , 25 , 31 , …”

“…Fourteen studies were conducted in Japan [ 22 , 27 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 43 , 45 , 50 , 51 ], nine in the USA [ 21 , 25 , 31 , 38 , 41 , 46 , 47 , 48 , 49 ], three in France [ 44 , 53 , 54 ], three in Italy [ 26 , 52 , 56 ], three in China [ 28 , 39 , 42 ], two in South Korea [ 24 , 55 ], one in Ireland [ 23 ], and one in Saudi Arabia [ 40 ]. The reported clinical endpoints included mortality in 21 studies [ 21 , 22 , 23 , 24 , 26 , 29 , 30 , 32 , 33 , 37 , 38 , 39 , 40 , 45 , 49 , 50 , 52 , 53 , 54 , …”

“…The reported clinical endpoints included mortality in 21 studies [ 21 , 22 , 23 , 24 , 26 , 29 , 30 , 32 , 33 , 37 , 38 , 39 , 40 , 45 , 49 , 50 , 52 , 53 , 54 , 55 , 56 ], disease exacerbation in 11 [ 22 , 23 , 25 , 27 , 28 , 31 , 34 , 37 , 41 , 46 , 55 ], disease progression in five [ 42 , 43 , 44 , 47 , 54 ], hospitalization in three [ 48 , 53 , 54 ], tolerability to the antifibrotic agent nintedanib in three [ 35 , 36 , 51 ], and incident pneumothorax in one [ 32 ]. Ten studies were prospective [ 25 , 26 , 27 , 28 , 30 , 43 , 44 , 46 , 53 , 54 ], while the remaining 26 were retrospective [ …”

“…Twenty-nine studies assessed the BMI as a continuous variable [ 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 43 , 45 , 46 , 47 , 48 , 51 , 52 , 53 , 54 , 55 , 56 ], six used cut-off values [ 24 , 36 , 38 , 42 , 44 , 49 ], and one assessed both [ 50 ]. Twenty-six out of 36 studies were published over the last five years [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , …”

“…The risk of bias was assessed as low in 20 studies [ 21 , 22 , 24 , 29 , 32 , 33 , 35 , 36 , 38 , 39 , 40 , 43 , 45 , 48 , 50 , 51 , 52 , 53 , 55 , 56 ] and high in the remaining 16 studies [ 23 , 25 , 26 , 27 , 28 , 30 , 31 , 34 , 37 , 41 , 42 , 44 , 46 , 47 , 49 , 54 ] ( Table 2 ).…”