ILD exacerbation studies Flashcards
describe the study by Jang et al 2021?
retrospective cohort study
single center
south korea
2016-2018
n=182
what were the baseline characteristics and inclusion/exclusion criteria for Jang et al 2021? how did they differ ILD type?
excluded: CHF, volume overload, PE, non-resp dyspnea, >1 month symptoms
- no PFT w/in 6 months
separated into IPF and non IPF
overall IPF sicker - worse PFTs, more baseline O2, lower P/F
IPF - 69, male (80%), 58% prior smoker, FVC 57%, DLCO 44%, 54% on antifibrotics, 23% on supplemental oxygen, 42% on prednisone at baseline, P/F 220
non-IPF - 67, 78% never smokers, FVC 67%, DLCO 49%, 0% on antifibrotics, 13% on supplemental O2, 65% on prednisone baseline, P/F 234
describe the major findings of the Jang et al 2021 cohort study
the IPF group got ~ 1 mg/kg pred, the non-IPF group got 1.1 mg/kg pred
in the all patients group and the non-ipf group > 1 mg/kg was associated with increased survival at 90 days. The trend was there but not significant in the IPF group.
additional predictors of 90 day mortality were need for ventilation and initial PF ratio.
no analysis was done by dose of prednisone beyond the 1 mg/kg stratification
no other agents were used (ritux, IVIG, cyclophosphamide)
steroid dosing ranged between .5-2 mg/kg and did not include pulse dosing outside of vasculitis or dermatomyositis
what is the clinical question and study design of the PANTHER-IPF study 2012?
randomized double blind placebo controlled multicenter study
1:1:1 randomization
combination therapy - prednisone, NAC, AZA n =77
- prednisone .5 mg/kg tapered to .15 mg/kg over 25 weeks
- AZA weight based, max 150 mg daily
- NAC 600 TID daily
placebo n = 78
NAC only
what were the key inclusion and exclusion criteria for the the PANTHER-IPF study 2012?
inclusion - IPF age 35-85 (diagnosed via biopsy or HRCT)
“mild to moderate impairment” - FVC > 50, DLCO > 30
exclusion
- obvious exposures, CTD, or emphysema that could cause fibrosis
- active infection
- unstable cardiac disease
- evidence of obstruction via PFTs (< .65), e/o BDR
- requirement for supplemental O2
- Cr 2x ULN, LFT abnormalities, unlikely to survive for non IPF reasons
what were the baseline characteristics of the participants in the PANTHER-IPF study 2012?
both groups
- age 68, 75% male, 97% white, 65% former smokers, mean FVC 70%, mean DLCO 43%
overall balanced
what were the notable outcomes of the PANTHER-IPF study 2012?
study was stopped early by the interim analysis for harm in the combination trial group
there were increased in deaths (8 vs 1) and hospitalizations (23 vs 7), exacerbations (5 vs 0)
interestingly there was NOT a difference in the composite outcome of death AND disease progression (FVC >10% drop), which ?indicates the placebo group was progressing but not dying?
what do Mari et al 2020 describe in their abstract “Methylprednisolone pulse therapy in Acute Exacerbations of Idiopathic Pulmonary Fibrosis” in ERJ?
retrospective chart review of AE-IPF patients admitted between 2014 and 2020
Study done in france
n= 26 total analyzed, 10 of which who died.’
Exposure was 1g methylpred x 3 days without information on follow up dosing.
HR .81 CI .2-3.1 benefiting steroids; ?initial benefit for first 2 weeks but gone by day 30.
abstract, no full text
what do Yamano et al 2018 describe in their paper “Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus?”
retrospective chart review of CTD-ILD patients in JAPAN. NOT DURING AN EXACERBATION
total n = 26
they reated 11 w/ RA, 9 w/ dermatomyositis, 4 w/ sjogrens and 2 others
overall found benefit
(FVC; 77.8% to 94.6%, P < 0.001), diffusing capacity of the lung for carbon monoxide (DLCO ; 66.1% to 75.1%, P < 0.001), 6-min walk distance (6MWD; 530 to 568 m, P = 0.02),
full text not available but there is a full paper
Guerra et al 2019 describe a 3 year follow up of AE in “F-ILD” - any ILD with UIP. what did they show in their abstract?
they followed F-ILDs for 3 years and identified 115 admissions among n = 47 patients
PORTUGAL
the most common ILDs were
cHP - 68%, CTD ILD 11%, IPF 10% and 3% drug related.
In hospital mortality was 21% for all comers
most exacerbations were caused by an infection - 75%
mortality was worse in IPF > CTD ILD > cHP
treatment data not described
abstract, there is no full text
Mori et al 2018 describe the difference in AE between iPAF and IIP in their abstract “Different characteristics and outcomes of acute exacerbation: comparison between interstitial pneumonia with autoimmune features and lone idiopathic interstitial pneumonia.” what did they report?
retrospective chart review of 157 cases of FIRST AE between 2010 and 2017.
n = 157 admissions, 79 were IPAF, 62 were IIP
IPAF group was younger (72 v 77), more likely to be female (45%) and less likely to have smoked (58%).
in hospital mortality 6.3 vs 42% in favor of IPAF
90 day mortality 9% and 52% in favor of IPAF
details of treatment not given
abstract, no full text
Kreuter et al 2018 describe outcome differences between IPF and non-IPF ILD in their abstract “Outcome differences between idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILD) - data from the EXCITING registry”
n = 601 total, 151 IPF (25%)
GERMAN registry
32% of all hospitalizations were IPF
46% of all deaths were IPF; time to death for IPF was 101 months vs 229 months
PFS (diagnoses to >10% fvc drop, hospitalization, or death) worse for IPF 62 months vs 113 months
abstract, no full text
Faverio et al 2019 describe AE outcomes in IPF vs non-IPF in their abstract “Differences of acute exacerbations in idiopathic pulmonary fibrosis compared to other fibrotic lung diseases”
DONE IN ITALY
Out of 48 patients, 31 had AE-IPF and 17 AE non-IPF (n=17). Although IPF patients were predominantly men and former smokers and non-IPF patients were mainly women and never-smokers, clinical presentation and laboratory findings were similar between groups. Lung function test did not differ, with the exception of DLCO% predicted at baseline that was lower in IPF compared to non-IPF subjects. In-hospital mortality of AE-IPF was higher than AE non-IPF (65% vs 29%, p=0.020). Finally, the diagnosis of IPF was the only independent factor that affected prognosis, with a risk of death increased by 78% in IPF patients.
abstract, no full text
the ATS cites Al-hameed et al 2004 in their recommendation for glucocorticoids for IPF. What is this study and what does it show?
retrospective cohort study among IPF ICU admissions at Manitoba hospital
n = 25
primary outcome - survival at hospital discharge
REQUIRED MECHANICAL VENTILATION, excluded infection
patient baseline FVC ~55%, DLCO 37% - measured in year prior to admission
All patients got ‘high dose steroids’ , all got antibiotics
8/25 got CYC
24/25 died, 1/25 readmitted and died
no information on steroid dosing
UTD cites Tachikawa et al 2012 review “Clinical Features and Outcome of Acute Exacerbation of Interstitial Pneumonia: Collagen Vascular Diseases-Related versus Idiopathic” - what was their study and what did they find?
single center retrospective cohort study for all admissions of AE-ILD over 6 years. excluded infection.
primary outcome 90 day mortality.
studied 47 IIP (13 IPF) vs 15 CTD-ILD (RA, dermato, SSc)
CTD-ILD were more likely to be younger, female, less hypoxic, on baseline immunosuppression
interventions offered were “high dose steroids”, antibiotics, CYC, polymyxin
steroid dosing not available
There was no sig diff in overall mortality though trend toward benefit in CTD-ILD (33 v 44%)
subgroun analysis demonstrated CTD-ILD 33% vs IPF 69%) was worse tho only 13 IPF pts
