Systematic review and meta-analysis of the prognosis and prognostic factors of interstitial pneumonia with autoimmune features

Abstract

Objective: To clarify the prognosis and prognostic factors of interstitial pneumonia with autoimmune features (IPAF) in comparison to idiopathic pulmonary fibrosis (IPF), the most common idiopathic interstitial pneumonia, and connective tissue disease-associated interstitial pneumonia (CTD-IP).

Design: A systematic review and meta-analysis.

Data sources: Electronic databases such as Medline and Embase were searched from 2015 through 6 September 2019.

Eligibility criteria for selecting studies: Primary studies that comparatively investigated the prognosis or prognostic factors of IPAF were eligible.

Data extraction and analysis: Two reviewers extracted relevant data and assessed the risk of bias independently. A meta-analysis was conducted using a random-effects model. The quality of presented evidence was assessed by the Grades of Recommendation, Assessment, Development, and Evaluation system.

Results: Out of a total of 656 records retrieved, 12 studies were reviewed. The clinical features of IPAF were diverse between studies, which included a radiological and/or pathological usual interstitial pneumonia (UIP) pattern of between 0% and 73.8%. All studies contained some risk of bias. There was no significant difference of all-cause mortality between IPAF-UIP and IPF in all studies, although the prognosis of IPAF in contrast to IPF or CTD-IP varied between studies depending on the proportion of UIP pattern. Among the potential prognostic factors identified, age was significantly associated with all-cause mortality of IPAF by a pooled analysis of univariate results with a hazard ratio (HR) of 1.06 (95% confidence interval (CI) 1.04 to 1.07). The adjusted effect of age was also significant in all studies. The quality of presented evidence was deemed as very low.

Conclusion: There was no significant difference of all-cause mortality between IPAF-UIP and IPF. Age was deemed as a prognostic factor for all-cause mortality of IPAF. The findings should be interpreted cautiously due to the low quality of the presented evidence.

Prospero registration number: CRD42018115870.

Keywords: Interstitial pneumonia with autoimmune features; meta-analysis; prognosis; review.

Figure 1

Study flow diagram A total of 656 records were retrieved through a search of four electronic databases, Medline, EMBASE, Science Citation Index Expanded, and Google Scholar. After removing 181 duplicates, 475 records were screened by titles and abstracts, which identified 109 ineligible articles composed of case reports (n=8), conference abstracts (n=58), letters or editorials (n=27), non-English reports (n=5) and review articles (n=11). After 335 more records were excluded due to irrelevant subjects, the remaining 31 records were retrieved as full texts, and finally 12 reports/studies, which included 3 studies conducted by the same research group, were eligible for this study. IPAF, interstitial pneumonia with autoimmune features.

Figure 2

Forrest plot of the effect of age on all-cause mortality of interstitial pneumonia with autoimmune features. The effect of age on all-cause mortality was reported in four studies, in which a total of 528 participants with 236 men (44.7%) were included. Meta-analysis of these studies demonstrated that age was significantly associated with all-cause mortality with an HR of 1.06 (95% CI 1.04 to 1.07, p<0.00001) with no heterogeneity.

Figure 3

Forrest plot of the effect of sex on all-cause mortality of interstitial pneumonia with autoimmune features. The effect of sex on all-cause mortality was reported in four studies, in which a total of 528 participants with 236 men (44.7%) were included. Meta-analysis of these studies demonstrated that all-cause mortality of men was significantly worse than that of women with an HR of 1.66 (95% CI 1.22 to 2.25, p=0.001) with no heterogeneity.

Figure 4

Forrest plot of the effect of smoking habit on all-cause mortality of interstitial pneumonia with autoimmune features. The effect of smoking habit was reported in five studies, in which a total of 585 participants with 265 men (45.3%) were included. Meta-analysis of these studies demonstrated that ever smokers were not significantly associated with all-cause mortality with an HR of 1.54 (95% CI 0.97 to 2.46, p=0.07/95% prediction interval 0.37 to 6.33). There was substantial heterogeneity between the results of the included studies (χ²=8.26, df=4, p=0.08, I²=52%). Only one study (Oldham et al 38) demonstrated an opposite effect to the others, and the majority of participants were ever smokers with a radiological usual interstitial pneumonia pattern in that study.

Figure 5

Forrest plot of the effect of a usual interstitial pneumonia (UIP) pattern on a high-resolution computed tomography (HRCT) and/or a surgical lung biopsy (SLB) specimen on all-cause mortality of interstitial pneumonia with autoimmune features (IPAF). The effect of UIP pattern on all-cause mortality was reported in six studies. Meta-analysis was conducted for three of these studies, in which a total of 430 participants with 195 men (45.3%) were included. A UIP pattern on HRCT and/or SLB was significantly associated with all-cause mortality of IPAF with an HR of 2.93 (95% CI 1.65 to 5.20, p=0.0002/95% prediction interval 0.01 to 808.7). There was moderate heterogeneity between the results of the included studies (χ²=3.44, df=2, p=0.18, I²=42%). Only one study (Dai et al 42) demonstrated a non-significant result, and it included the least proportion (4.5%) of IPAF subjects with a radiological and/or pathological UIP pattern in contrast to 54.6% and 36.7% in the other two studies (Oldham et al and Kim et al 48), respectively.

Figure 6

Forrest plot of the effect of percentage of predicted forced vital capacity (%FVC) on all-cause mortality of interstitial pneumonia with autoimmune features (IPAF). The effect of %FVC on all-cause mortality was reported in three studies, in which a total of 351 participants with 158 men (45.0%) were included. Meta-analysis of these studies demonstrated that %FVC was significantly associated with all-cause mortality of IPAF with an HR of 0.89 (95% CI 0.81 to 0.98, p=0.02) with no heterogeneity.

Figure 7

Forrest plot of the effect of percentage of diffusing capacity of the lung for carbon monoxide (%DLCO) on all-cause mortality of interstitial pneumonia with autoimmune features (IPAF). The effect of %DLCO on all-cause mortality was reported in three studies, in which a total of 351 participants with 158 men (45.0%) were included. Meta-analysis of these studies demonstrated that %DLCO was significantly associated with all-cause mortality of IPAF with an HR of 0.77 (95% CI 0.69 to 0.85, p<0.00001) with no heterogeneity.