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)

Conclusion

In summary, our results demonstrated that the coinfection is significantly associated with an enhanced risk of death by AE in IPF. Furthermore, this study reveals bacterial and viral co-infection as novel prognostic marker in the treatment of IPF. Further analysis is necessary in order to confirm these findings in a larger cohort of IPF patients.

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Abbreviations
IPF: Idiopathic pulmonary fibrosis; PCA: Principal component analysis; AE-IPF: Acute exacerbations in IPF; NPL: Nasopharyngeal lavage; BAL: Bronchoalveolar lavage; FVC: Forced vital capacity; FEV1: Forced expiratory volume 1; DLCO: Diffusion lung capacity for carbon monoxide; RSV: Respiratory syncytial virus.

Acknowledgements
The authors deeply acknowledge all the patients who contributed to this study. Also, authors are greatly thankful to the director and staff of all Hospitals for their valuable helps.

Funding
This work was supported by KUMS by grant number 97694. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Availability of data and materials
The datasets used and/or analyzed during the current study could become available through the corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
Ethical approval for this study was obtained from Kermanshah University of Medical Sciences (IR.KUMS.REC.1397.764). We confirm that written informed consent to participate was obtained from all of the participants in our study. We acquired permissions and/or licenses to access the clinical/personal patient data used in our research from Kermanshah University of Medical Sciences.

Consent for publication
Not applicable.

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