Inhaled Corticosteroids and the Risk of
Pneumonia
Tobias Welte
Department of Respiratory Medicine
ICS in COPD – A Risk Factor for CAP?
Rate of pneumonia in ICS Studies
1Calverley
P. NEJM 2007; 356: 775-89; 2Kardos P. AJRCCM 2007; 175: 144-49; 3Wedzicha JA; AJRCCM 2008; 177: 19-26
TORCH1
3-year Follow-Up
Placebo
Salmeterol
or
Tiotropium
Fluticason
Seretide
(SAL/FLU)
12.3%
13.3%
18.3%*
19.6%*
VIVACE2
44 week FollowUp
7 (=1.5%)
23 (=5.7%)
INSPIRE3
2-year Follow-Up
24 (=4%)
50 (=8%)§
*p< 0.001 vs. Placebo; § Hazard Ratio for time to reported pneumonia 1.94 (p=0.008)
Welte – ICS and pneumonia 11.10.2014
Steroid Use in COPD - A Risk Factor for CAP?
Ernst P. AJRCCM 2007; 176: 162-66
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175,906 patients with COPD, 23,942 hospitalized for pneumonia (1.9 per 100 per year)
Matched to 95,768 control subjects.
The adjusted RR of hospitalization for pneumonia associated with current use of ICS was
1.70 (95% CI), 1.63–1.77) and 1.53 (95% CI, 1.30–1.80) for pneumonia hospitalization
followed by death within 30 days. The RR of hospitalization
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greatest with the highest doses of ICS equivalent to fluticasone at 1,000 µg/day or more (RR,
2.25;95% CI, 2.07–2.44).
All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they
had received ICS (7.4 and 8.2%, respectively)
Welte – ICS and pneumonia 11.10.2014
Steroid Use in COPD - A Risk Factor for CAP?
Suissa S. Thorax 2013; 68: 1029-36
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New-user cohort of patients with COPD
treated during 1990–2005.
A nested case–control analysis was used
to estimate the rate ratio (RR) of serious
pneumonia associated with current ICS
use
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adjusted for age, sex, respiratory disease
severity and comorbidity.
163 514 patients, of which 20 344 had a
serious pneumonia event during the 5.4
years of follow-up (incidence rate
2.4/100/year)
Use of ICS was associated with a 69%
increase in the rate of serious pneumonia
(RR 1.69)
The risk was sustained with long-term
use and declined gradually after stopping
ICS use, disappearing after 6 months
The rate of serious pneumonia was
higher with fluticasone (RR 2.01),
increasing with the daily dose, but was
much lower with budesonide (RR 1.17)
Welte – ICS and pneumonia 11.10.2014
Fluticasone
Budesonid
Steroid Use in COPD - A Risk Factor for CAP?
Suissa S. Thorax 2013; 68: 1029-36
Welte – ICS and pneumonia 11.10.2014
Budesonide and the Risk of Pneumonia in COPD – a
Meta-Analysis
D SIn et al., Lancet 374:712-719, 2009
Risk of pneumonia as SAE
Welte – ICS and pneumonia 11.10.2014
BMJ 2013;346: f3306
Welte – ICS and pneumonia 11.10.2014
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Cumulative number of pneumonia events and admissions to
hospital because of pneumonia per patient over nine
years after index date
Janson C. et al. BMJ 2013;346: f3306
Welte – ICS and pneumonia 11.10.2014
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Pneumonie related Mortality
Janson C. et al. BMJ 2013;346: f3306
Welte – ICS and pneumonia 11.10.2014
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Steroid Use in COPD - A Risk Factor for CAP?
Eurich DT. CID 2013; 57: 1138-44
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Clinical and 5-year follow-up data were
collected on all adults aged ≥65 years
with pneumonia over a period of 2 years.
Nested case-control design matched on
age, sex, and COPD
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Cases
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Controls
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free of pneumonia
653 recurrent pneumonia cases were
matched with 6244 controls
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patients with recurrent pneumonia ≥30 days
after initial episode
Mean age was 79 years
3577 (52%) male
2652 (38%) had COPD
2294 (33%) ever used ICS
123 of 870 (14%) current ICS users had
recurrent pneumonia compared to 395 of
4603 (9%) never-users (adjusted odds
ratio, 1.90; P < .001; number need to
harm = 20)
no association between past use of ICS
and pneumonia: 9% of past users versus
9% never-users (P = .36).
Welte – ICS and pneumonia 11.10.2014
Eurich DT. CID 2013; 57: 1138-44
Welte – ICS and pneumonia 11.10.2014
Steroid Use in COPD - A Risk Factor for CAP?
McKeever T. Chest 2013; 144: 1788-94
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Primary care data from The Health Improvement Network in the UK
People with asthma with pneumonia or lower respiratory tract
infection
Age- and sex-matched control subjects.
The highest strength of ICS ( >1,000 µg) had a 2.04 increased risk of
pneumonia or LTRI compared with no prescription for ICS within the
previous 90 days
Welte – ICS and pneumonia 11.10.2014
ICS – Risk for Tuberculosis
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Chang-Hoon L. et al. Thorax 2013;68:1105–1113.
Case control study in Korea using
the national health care data base
853 439 Pts prescribed ICS for the
first time (2007 bis 2010)
Pts with a first diagnosis of TB
after starting ICS were included
Data were adjusted for age,
gender, Asthma-/COPD Diagnosis
and time since start of ICS
4139 TB were diagnosed and
compared with 20 583 controls
ICS increased the likelihood for Tb
(adjusted OR 1.20) significantly
The assoziation was dose
dependend (p <0.001)
Welte – ICS and pneumonia 11.10.2014
ICS – Risk for NTM
CAndréjak C. et al. Thorax 2013;68: 256–62.
• Case-control study in adults in Denmark with microbiologically
confirmed NTM pulmonary disease between 1997 and 2008
• 10 matched population controls per case.
• Chronic respiratory disease was associated with a 16.5-fold
increased risk of NTM pulmonary disease
• Adjusted OR for NTM disease was 15.7 for COPD, 7.8 for
asthma, 9.8 for pneumoconiosis, 187.5 (95% for bronchiectasis,
and 178.3 for tuberculosis history
• ORs were 29.1 for patients with COPD on current ICS therapy
and 7.6 for patients with COPD who had never received ICS
therapy
• ORs increased according to
• ICS dose from 28.1 for low-dose intake to 47.5 for high-dose
intake (more than 800 μg/day)
• OR was higher for fluticasone than for budesonide
Welte – ICS and pneumonia 11.10.2014
ICS and Pneumonia
Pleural Effusion
Sellares J. et al. AJRCCM 2013: 1241-48.
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Single center cohort study in Spain in 3,612 CAP patients
633 Pts (17%) were treated with ICS before CAP was diagnosed (COPD
54%; Asthma, 13%)
Incidence of a parapneumonic pleural effusion lower in ICS patiens
compared to non ICS patients (5% vs. 12%; P < 0.001).
ICS pretreatment was associated with higher glucose and pH and
lower protein and LDH concentraitions in the pleural effusion
Welte – ICS and pneumonia 11.10.2014
ICS and Pneumonia
Pleural Effusion
Sellares J. et al. AJRCCM 2013: 1241-48.
Welte – ICS and pneumonia 11.10.2014
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Welte – ICS and pneumonia 11.10.2014