1. Inhaled Corticosteroids and the Risk of Pneumonia Tobias Welte Department of Respiratory Medicine

2. ICS in COPD – A Risk Factor for CAP? Rate of pneumonia in ICS Studies
1Calverley P. NEJM 2007; 356: ; 2Kardos P. AJRCCM 2007; 175: ; 3Wedzicha JA; AJRCCM 2008; 177: 19-26
Placebo
Salmeterol or Tiotropium
Fluticason
Seretide
(SAL/FLU)
TORCH1
3-year Follow-Up
12.3%
13.3%
18.3%*
19.6%*
VIVACE2
44 week Follow-Up
7 (=1.5%)
23 (=5.7%)
INSPIRE3
2-year Follow-Up
24 (=4%)
50 (=8%)§
*p< vs. Placebo; § Hazard Ratio for time to reported pneumonia 1.94 (p=0.008)

3. Steroid Use in COPD - A Risk Factor for CAP?
Ernst P. AJRCCM 2007; 176:
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
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)

4. Steroid Use in COPD - A Risk Factor for CAP?
Suissa S. Thorax 2013; 68:
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
adjusted for age, sex, respiratory disease severity and comorbidity.
patients, of which 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)
Fluticasone
Budesonid

5. Steroid Use in COPD - A Risk Factor for CAP?
Suissa S. Thorax 2013; 68:

6. Budesonide and the Risk of Pneumonia in COPD – a Meta-Analysis
D SIn et al., Lancet 374: , 2009
Risk of pneumonia as SAE

7. BMJ 2013;346: f3306 44

8. 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 44

9. Pneumonie related Mortality
Janson C. et al. BMJ 2013;346: f3306 44

10. Steroid Use in COPD - A Risk Factor for CAP?
Eurich DT. CID 2013; 57:
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
Cases
patients with recurrent pneumonia ≥30 days after initial episode
Controls
free of pneumonia
653 recurrent pneumonia cases were matched with 6244 controls
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).

11. Eurich DT. CID 2013; 57:

12. Steroid Use in COPD - A Risk Factor for CAP?
McKeever T. Chest 2013; 144:
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

13. ICS – Risk for Tuberculosis
Chang-Hoon L. et al. Thorax 2013;68:1105–1113.
Case control study in Korea using the national health care data base
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 controls
ICS increased the likelihood for Tb (adjusted OR 1.20) significantly
The assoziation was dose dependend (p <0.001)

14. 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 for COPD, 7.8 for asthma, 9.8 for pneumoconiosis, (95% for bronchiectasis, and 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

15. ICS and Pneumonia Pleural Effusion
Sellares J. et al. AJRCCM 2013:
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

16. ICS and Pneumonia Pleural Effusion
Sellares J. et al. AJRCCM 2013: 45