Bacterial and Viral Coinfection in Idiopathic Pulmonary Fibrosis Patients

The Prevalence and Possible Role in Disease Progression

Mohsen Moghoofei; Shayan Mostafaei; Nasim Kondori; Michelle E. Armstrong; Farhad Babaei

BMC Pulm Med. 2022;22(60)

Abstract and Introduction

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia of unknown aetiology with a mean survival rate of less than 3 years. No previous studies have been performed on the role of co-infection (viral and bacterial infection) in the pathogenesis and progression of IPF. In this study, we investigated the role of viral/bacterial infection and coinfection and their possible association with pathogenesis and progression of IPF.

Methods: We investigated the prevalence and impact of bacterial and viral coinfection in IPF patients (n = 67) in the context of pulmonary function (FVC, FEV₁ and DL_CO), disease status and mortality risk. Using principal component analysis (PCA), we also investigated the relationship between distribution of bacterial and viral co-infection in the IPF cohort.

Results: Of the 67 samples, 17.9% samples were positive for viral infection, 10.4% samples were positive for bacterial infection and 59.7% samples were positive coinfection. We demonstrated that IPF patients who were co-infected had a significantly increased risk of mortality compared (p = 0.031) with IPF patients who were non-infected [Hazard ratio: 8.12; 95% CI 1.3–26.9].

Conclusion: In this study, we report for the first time that IPF patients who were coinfected with bacterial and viral infection have significantly decreased FVC and DL_CO (% predicted). Besides, the results demonstrated the increased AE-IPF, increased incidence of death and risk of mortality in infected/coinfected patients compared to non-infected IPF patients.

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Abstract and Introduction
Background
Methods
Results
Discussion
Conclusion
References

Table 1. Baseline characteristics of the IPF patients (n = 67)
Characteristics
Age (year)*	62.8 ± 12.44
FVC*	75.3 ± 4.37
FEV₁*	70.9 ± 4.30
DL_CO*	70.5 ± 3.96
Sex⁺
Male	40 (59.7)
Female	27 (40.3)
Disease status⁺
Acute exacerbation	55 (82.1)
(AE-IPF) stable	12 (17.9)
Immunosuppression drugs⁺
Pred 5 mg	2 (3)
Pred 10 mg	5 (7.5)
Pred 20 mg	2 (3)
CyA 125 mg	2 (3)
Unknown	8 (11.9)
Surgical lung biopsy⁺
No	63 (94)
Yes	4 (6)
History of fibrosis in family⁺
No	55 (82.1)
Yes	12 (17.9)
Bacterial infection No. 7 (10.4%)
P. aeruginosa ⁺	17 (27)
S. pneumonia ⁺	17 (27)
S. aureus ⁺	16 (25.4)
K. pneumoniae ⁺	16 (25.4)
H. influenzae ⁺	29 (46)
Viral infection No. 12 (17.9%)
Parainfluenza⁺	12 (19)
Influenza⁺	12 (19)
Adeno⁺	10 (15.9)
Rhinovirus⁺	25 (39.7)
RSV⁺	15 (23.8)
Coronavirus⁺	9 (14.3)
Co-infection⁺ No. 40 (59.7%)
Death⁺
No	49 (73.1)
Yes	18 (26.9)

Ref. considered as the reference level for each categorical variable, NA not available, forced vital capacity, FVC forced expiratory volume 1, FEV₁, diffusing capacity of lung for carbon monoxide: DL_C0
*Indicated as mean ± standard deviation
⁺Indicated as "n" (%)

Table 2. Comparison of pulmonary function indices between non-infected, bacterial-, viral- and co-infected IPF patients, respectively
PFT index	Non-infected Group 1 (n = 8)	Bacterial Infection Group 2 (n = 7)	Viral Infection Group 3 (n = 12)	Coinfection Group 4 (n = 40)	R, Adj. p*	R, Adj. p ⁺	R, Adj. p ^$
FVC	79.7 ± 3.30	76.6 ± 5.19	77.8 ± 2.88	73.7 ± 4.08	0.961, 0.368	0.976, 0.652	0.924, 0.013
FEV₁	73.5 ± 5.0	73.1 ± 5.55	73.1 ± 3.39	69.5 ± 3.82	0.994, 0.996	0.994, 0.992	0.945, 0.152
DL_CO	76.5 ± 1.29	71.7 ± 4.64	71.2 ± 2.73	69.3 ± 3.70	0.937, 0.076	0.93, 0.030	0.905, 0.001

Data represents Mean ± SD
IPF uninfected patients are considered as the reference group (Group 1). The Adj. P is based on the marginally adjusted p values by the Benjamini–Hochberg-FDR correction at α = 0.05. Bold values indicated as statistically significant at p < 0.05 level
PFT pulmonary function test, R ratio
*Comparison between group 2 versus group 1
⁺Comparison between group 3 versus group 1
^$Comparison between group 4 versus group 1

Table 3. Comparison of disease status, survival time and death occurrence between non-infected, bacterial-, viral- and co-infected IPF patients, respectively
Characteristics	Non-infected Group 1 (n = 8)	Bacterial Infection Group 2 (n = 7)	Viral Infection Group 3 (n = 12)	Coinfection Group 4 (n = 40)	p*	p ⁺	p ^$
Disease status⁻ (acute vs. stable)	0	1 (14.3)	1(8.3)	22 (55)	0.675	0.930	< 0.001
Death status⁻ (death vs. survive)	0	2 (28.5)	0	15 (37.5)	0.40	0.622	0.043
Survival time⁺ (months-to-death)	42.5 ± 6.55	38.5 ± 7.02	34.4 ± 2.83	32.9 ± 9.12	0.426	0.193	0.026

Disease- and death-status are indicated as "n" (%). Survival time is indicated as median ± IQR
IPF uninfected patients are considered as the reference group (Group 1). Bold values indicated as statistically significant at p < 0.05 level. Follow up period is 60 months
*Comparison between group 2 versus group 1
⁺Comparison between group 3 versus group 1
^$Comparison between group 4 versus group 1