Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Table 1 Community-acquired pneumonia in patients administered proton pump inhibitors based on dose and duration of use

	Cases of PNA (%)	Controls w/o PNA (%)	OR
Acid suppression w/in 30-180 d	3.4 (7.2)	346 (7.0)	1
DDD of PPI administered
< 1	25 (5.3)	265 (5.3)	1.23
1	59 (12.4)	358 (7.2)	1.94a
> 1	15 (3.2)	74 (1.5)	2.28 a
Duration of PPI use (d)
< 30	27 (5.7)	157 (3.2)	2.24 a
30-180	40 (8.4)	291 (5.9)	1.65 a
> 180	32 (6.7)	249 (5.0)	1.52 a

Adapted from Laheij et al. As the daily dose of PPI increases, the odds ratio of pneumonia increases. However, as the duration of PPI use increases, the odds ratio of pneumonia decreases.

^aP < 0.05.

Table 2 Community-acquired pneumonia based on age and current proton pump inhibitor use

Age group	Current PPI use			Not Currently using PPIs			OR
	Acquired PNA	Controls w/o PNA	Acquired PNA (%)	Acquired PNA	Controls w/o PNA	Acquired PNA (%)
< 40 yr	30	29	51	2094	8986	19	2.3a
> 40-60 yr	107	127	46	883	4321	17	2.0a
> 60 yr	681	1427	32	3848	19285	17	1.5a

Adapted from Gulmez et al. The odds ratio of community-acquired pneumonia decreases as the age of the patient population increases. The percentage of pneumonia decreases as the patient population ages; however, there is no change in the percentage of community-acquired pneumonia in patients not currently using proton pump inhibitors as the age of the patient population increases.

^aP < 0.05.

Table 3 Community-acquired pneumonia based on proton pump inhibitor exposure

PPI exposure	Case patients	Control participants	Odds Ratio	P value
No PPI exposure	73 187	777 626	1	-
No PPI exposure in 30 d	3424	19 215	0.95	0.05
Current PPI exposure	3455	10 031	1.02	0.48
< 1.5 DDD	3056	9126	1	0.94
> 1.5 DDD	399	905	1.23	0.01
Duration of PPI Use (d)
< 2	64	54	6.53	< 0.001
< 7	124	148	3.8	< 0.001
< 14	204	288	3.16	< 0.001
< 30	469	1100	1.74	< 0.001
30-180	940	2447	1.09	0.11
>180	2046	6484	0.91	0.01

Adapted from Sarkar et al. As the daily dose of proton pump inhibitors administered to patients increases, the odds ratio for community-acquired pneumonia increases. Exposure greater than 1.5 times the defined daily dose (DDD) achieved statistical significance. Secondly as the duration of use decreases, the odds ratio of community-acquired pneumonia increases suggesting that there may be some confounding factors with starting proton pump inhibitor therapy and pneumonia. DDD: defined daily dose.

Table 4 Rate of Hospital-Acquired Pneumonia based on Acid-Suppressive Medication

Characteristic	Acid-suppressive exposure	No acid-suppressive exposure	Unadjusted OR (95% CI)	Adjusted OR (95% CI)
	PPI
Total admissions	25 374	30 956	56 330	56 330
HAP (%)	1340 (5.3)	610 (2.0)	2.8 (2.5-3.1)	1.3 (1.1-1.4)
	H2RA
Total admissions	5686	30 956	36 642	36 642
HAP (%)	176 (3.1)	610 (2.0)	1.6 (1.3-1.9)	1.2 (0.98-1.4)

Adapted from Herzig et al. Based on the acid-suppressive therapy administered within the first 48 h of a hospital admission, the odds ratio of hospital-acquired pneumonia varies. The risk of pneumonia is highest following exposure to proton pump inhibitors.

Table 5 Hospital-acquired pneumonia according to acid-suppressive exposure

Outcome	Acid-suppressive exposure (%)	No acid-suppressive exposure (%)	Adjusted OR (95% CI)	Propensity-matched
Number of patients	32 922	30 956	63 878	32 792
HAP	1609 (4.9)	610 (2.0)	1.3 (1.1-1.4)	1.3 (1.1-1.4)
Aspiration PNA	361 (1.1)	112 (0.4)	1.4 (1.1-1.8)	1.4 (1.1-1.8)
Non-Aspiration PNA	1262 (3.8)	501 (1.6)	1.2 (1.1-1.4)	1.2 (1.1-1.4)

Adapted from Herzig et al. There was a stronger association between pneumonia and acid-suppressive exposure than with pneumonia and no acid-suppressive exposure regardless of the type of pneumonia the patient acquired. Exposure was defined as at least one administration during the course of the hospitalization.