Determinants of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone,Northwest Ethiopia: A case control study

Abstract

Background

Asthma and pneumonia are common respiratory conditions worldwide. Pneumonia is a life-threatening lung infection and a frequent comorbidity among adult asthmatic patients, often causing hospital admission. Despite the global burden, evidence on determinants of pneumonia among adult asthmatic patients in Ethiopia is limited.

Objective

This study aimes to identify determinants of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia.

Methods

A multicenter unmatched case-control study was conducted from August 20 to October 25, 2025 among 359 adult asthmatic patients (120 cases and 239 controls) in public hospitals of Awi Zone, Northwest Ethiopia. Eligible participants were adults aged ≥18 years with ≥6 months asthma diagnosis and ≥3 months follow-up. Cases were asthmatic patients with pneumonia, and controls were those without pneumonia. Patients with COPD and newly diagnosed asthma were excluded. Participants were selected consecutively. Data were collected using interviewer-administered questionnaires and medical records. Determinants were identified using bivariable and multivariable logistic regression, with statistical significance set at p<0.05.

Results

Cases were older than controls, with mean ages of 60.25 ± 15.36 and 44.85 ± 11.04 years, respectively. In multivariable analysis, demographic, behavioral, and clinical factors were associated with pneumonia. Increasing age (AOR = 1.06, 95% CI: 1.01–1.10) and current alcohol use (AOR = 2.93, 95% CI: 1.03–4.38) increased the odds. Prior hospital admission for acute asthma exacerbation showed the strongest association (AOR = 13.22, 95% CI: 9.55–19.51). Inhaled corticosteroid use (AOR = 4.06, 95% CI: 3.16–7.23) and loss of follow-up (AOR = 4.48, 95% CI: 3.42–7.16) were also associated with higher odds, while controlled asthma was protective (AOR = 0.06, 95% CI: 0.02–0.16).

Conclusion

Age, alcohol use, prior hospitalization, inhaled corticosteroid use, and irregular follow-up increased pneumonia risk, while controlled asthma was protective. Strengthening follow-up and interventions may reduce pneumonia among asthmatic patients.

Keywords

pneumonia asthma determinants awi zone northwest Ethiopia

Introduction

Asthma is a chronic inflammatory airway disease affecting both children and adults, with an estimated 300 million people affected worldwide.¹ It is a major cause of morbidity and health care utilization and contributes significantly to global disease burden measured in disability adjusted life years (DALYs).² In Ethiopia, asthma remains an important public health problem with a prevalence of 9.1%.³

Pneumonia is an acute infection of the lung parenchyma characterized by clinical features such as cough, fever, chest pain, and shortness of breath, supported by physical examination and radiologic findings.⁴ Community acquired pneumonia is the most common form and is an important cause of hospital admission and mortality, particularly among adults with underlying chronic conditions.^5,6

Evidence suggests that pneumonia occurs more frequently among patients with asthma compared with the general population.⁷ Asthma has been associated with increased susceptibility to respiratory infections and higher rates of pneumonia related hospitalization.^7,8 In addition, pneumonia in asthmatic patients is associated with increased risk of asthma exacerbations and increased health care utilization.⁹

Several studies have identified factors associated with pneumonia among asthmatic patients. These include older age, cigarette smoking, alcohol use, poor oral hygiene, presence of chronic comorbidities, and frequent use of inhaled corticosteroids.^7,10–13 Despite this evidence, data on determinants of pneumonia among adult asthmatic patients remain limited in low-income settings, including Ethiopia. Moreover, understanding these determinants is essential for guiding targeted prevention strategies and improving clinical outcomes in this vulnerable population. Therefore, this study aimed to assess the determinants of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia.

Methods and materials

Study area, design and period

This multicenter institution based unmatched case-control study was conducted in five public hospitals of Awi Zone, Northwest Ethiopia. Data were collected from August 20 to October 25, 2025 among adult asthmatic patients who had at least three months of follow up at chronic care clinics. Awi Zone is located 122 kilometers from Bahir Dar, the capital city of the Amhara Region, and 445 kilometers from Addis Ababa, the capital city of Ethiopia. The zone is administratively divided into 233 kebeles, the smallest administrative units in Ethiopia, and has a total population of more than 1.23 million according to zonal administrative data. The study was conducted in all five government hospitals found in the zone, namely Injibara General Hospital, Chagni Primary Hospital, Dangila Primary Hospital, Gimja Bet Primary Hospital, and Jawi Primary Hospital.

Population

The source population includes all adult asthmatic patients with age 18 years or above attending at chronic care outpatient department at public hospitals of Awi Zone and the study population were adult asthmatic patients with age ≥18 years who have follow up at chronic care outpatient department of 5 hospitals during the data collection period who fulfilled the inclusion criteria.

Eligibility criteria

Cases: Adult patients with asthma who had been diagnosed with asthma for at least six months, were diagnosed with pneumonia, and had at least three months of follow up at the chronic care outpatient department during the study period were included as cases.

Controls: Adult patients with asthma who had been diagnosed with asthma for at least six months, had no diagnosis of pneumonia, and had at least three months of follow up at the chronic care outpatient department during the study period were included as controls.

Exclusion criteria: Adult asthmatic patients diagnosed with asthma within the previous six months, with or without pneumonia, and referred from the outpatient department were excluded to minimize selection bias. In addition, patients with a documented history of chronic obstructive pulmonary disease (COPD) identified through medical record review were excluded from the study.

Sample size determination

The sample size was determined using the double population proportion formula in Epi Info version 7.2.5.0, with a 95% confidence level, 80% power, and a case-to-control ratio of 1:2. Variables that were significantly associated with pneumonia in a previous study conducted in Korea,¹⁴ including inhaled corticosteroid use, seeking care at a tertiary hospital, and comorbidity index, were used to calculate the sample size. Based on these variables, the maximum sample size was obtained from inhaled corticosteroid use, where 53.38% of cases and 36.4% of controls were exposed, that gave a sample size of 326 (109 cases and 217 controls). By considering a 10% non-response rate, the final sample size became 359, including 120 cases and 239 controls.

Sampling technique and procedure

The total sample size of 359 participants, comprising 120 cases and 239 controls, was proportionally allocated to the five public hospitals in Awi Zone based on the estimated two-month follow up flow of adult asthmatic patients in each facility. Injibara General Hospital was allocated 147 participants (49 cases and 98 controls) based on an estimated flow of 236 patients. Among the primary hospitals, Chagni Primary Hospital contributed 62 participants (21 cases and 41 controls) from 100 estimated patients, Dangila Primary Hospital contributed 56 participants (19 cases and 37 controls) from 90 patients, Jawi Primary Hospital contributed 50 participants (17 cases and 33 controls) from 80 patients, and Gimja Bet Primary Hospital contributed 44 participants (14 cases and 30 controls) from 70 patients. At each hospital, eligible participants were selected using consecutive sampling. All adult asthmatic patients with and without pneumonia who met the inclusion criteria were enrolled sequentially during follow up visits until the allocated sample size for each hospital was achieved (Figure 1).

Figure 1.

a sampling procedure for selecting study participants for identifying determinants of pneumonia among adult asthmatics attending public hospitals of Awi Zone, Northwest Ethiopia, 2025.

Study variables

The dependent variable of the study was pneumonia among asthmatic patients, categorized as cases and controls. The independent variables included socio-economic factors (age, sex, place of residence, occupation, educational status, marital status, average monthly household income, family size, presence of children in the household), lifestyle and behavioral factors (smoking, alcohol consumption, physical activity, oral hygiene, and body mass index), previous medical history (diabetes mellitus, cardiovascular disease, chronic liver disease, recent tooth and gum disease, tonsillectomy, recent upper respiratory tract infections, recent any type of respiratory tract infections, previous radiologically confirmed pneumonia, and history of hospital admission in past 1 year), environmental factors (occupational exposure to dust, contact with animals, and type of cooking fuel used), and asthma-related clinical factors (type of corticosteroid used, family history of asthma, recent hospital admission due to asthma exacerbation, duration of asthma diagnosis, follow-up status, frequency of inhaled medication use, and asthma control status).

Operational definitions

Adult: - an individual whose age was 18 years and above.

Asthmatic: - patients who have had a confirmed bronchial asthma diagnosed by physician clinically or lung function test or those who have had history of taking either short acting or long-acting anti-asthmatic medications for the treatment purpose of asthma.¹⁵

Pneumonia- was defined as a lower respiratory tract infection characterized by acute onset of symptoms such as cough, fever, chills or rigors, fatigue, dyspnea, and pleuritic chest pain, with radiological evidence of new pulmonary infiltrate on chest radiography, and diagnosed and documented by the treating physician based on standard clinical diagnostic criteria.¹⁶

Cases- Asthmatic adult patients with pneumonia confirmed by chest radiography (having new pulmonary infiltrate) who would have follow up in a chronic care outpatient department.

Controls- asthmatic adult patients without pneumonia who would have follow up in the chronic care outpatient department.

Alcohol consumption- participants history of drinking any type of alcohol containing drinks during their life time was assessed with response of yes/no, and participants with history of drinking any type of alcohol containing drinks with at least having one drink/day for at least once a week in the past 30 days prior to study were coded as current alcohol drinkers.¹⁷

Smoking status- current cigarette smokers was those who smoke at least one cigarette per day for at least 6 months. Former smokers were those who stopped smoking more than 6 months prior to the study.¹⁸

Physical activity- the patients were considered physically active if they involved in any combination of walking, moderate or vigorous intensity activities achieving a minimum total physical activity of at least 3000 metabolic equivalent of tasks (MET) minutes a week (high level), at least 600 MET minutes a week (moderate level) in either at work, leisure time, or commuting from place to place, otherwise, they were regarded as low level.¹⁹

Body mass index (BMI) - calculated as the weight divided height squared, and participants were considered underweight if (BMI <18.5 Kg/m²), normal weight if (BMI: 18.5 - 24.9 Kg/m²), overweight if (BMI: 25 - 29.9 Kg/m²), and obese if (BMI ≥30 Kg/m²).²⁰

Duration of asthma- a self-reported duration of patients being diagnosed with bronchial asthma for the first time by treating physician or health care provider.

Family history of asthma- a self-reported history of bronchial asthma occurred in parents or siblings that occurred at 18 years of age and younger.

Asthma control status - Participants in the study with scores greater than 19 were deemed to have controlled asthma, while those with scores less or equal to 19 were regarded to have uncontrolled asthma-based Asthma Control Test (ACT) tool which includes five questions with maximum score of 25 for the past four weeks.²¹

Data collection tools and procedures

Adult asthmatic patients attending chronic care follow-up clinics in five public hospitals of Awi Zone were approached during their routine clinic visits within the data collection period. Patients were screened for eligibility based on their medical records and inclusion criteria. Eligible participants were then classified as cases (asthma with pneumonia) or controls (asthma without pneumonia). Data were collected at a single point in time using exit interviews and medical record review. There was no longitudinal follow-up of participants after recruitment, as exposure and outcome were assessed concurrently at the time of clinic attendance. Data were collected in a quiet and private space by trained data collectors using a structured interviewer administered questionnaire. The questionnaire was administered using the KoboCollect mobile application to facilitate electronic data capture and improve data quality.

Physical activity was assessed using the International Physical Activity Questionnaire Short Form (IPAQ-SF). This tool captures walking, moderate, and vigorous-intensity activities performed at work, during house or yard work, for transportation, or for recreation and sport. Participants were asked to recall activities performed in the seven days preceding the interview. Adherence to physical activity was categorized as high, moderate, or low following the IPAQ screening protocol.^10,19,22

Anthropometric measurements were conducted following standard procedures. Height was measured to the nearest centimeter using a stadiometer with participants standing upright, and weight was measured in light clothing using a calibrated Seca digital weighing scale, recorded to the nearest 0.1 kg. The scale was regularly calibrated, and zero readings were checked before each measurement.

Asthma control status was assessed using the validated Asthma Control Test (ACT), a self-administered questionnaire comprising five items that evaluate activity limitation, shortness of breath, night time symptoms, use of rescue medication, and patient-rated asthma control over the previous four weeks. Each item is scored from 1 (worst) to 5 (best), with a total score ranging from 5 to 25. A score of ≥20 indicates well-controlled asthma.^15,21,23

Data quality control

Data collectors and supervisors were recruited from hospital health professionals and received one day training prior to data collection to ensure data quality. The reliability of the questionnaire in assessing determinants of pneumonia among asthmatic patients was evaluated using Cronbach’s alpha (α = 0.82). Before the main study, the tool was pretested on 5% of the total sample (Burie Primary Hospital), and the final questionnaire was refined based on the pretest findings. An additional question was included to clearly differentiate cases from controls using patient charts. Weight and height measurements were conducted by data collectors under the close supervision of doctors and nurses in the chronic clinic to minimize measurement and observation bias. Supervisors also conducted daily random checks of data collectors’ work for consistency and completeness, and all completed questionnaires were reviewed daily.

Data processing and analysis

Collected data were exported to Stata/MP version 17 for cleaning and analysis. Data quality was checked through visualization, frequency calculations, and sorting. Descriptive analysis was performed using frequencies and percentages for categorical variables, while mean and standard deviation (SD) were computed for continuous variables with normal distribution, after checking the normality assumption. The study was reported according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guideline.²⁴

Bivariable binary logistic regression analysis was performed to identify candidate variables for multivariable analysis. Variables with a p value <0.2 in the bivariable analysis were considered eligible for inclusion in the multivariable binary logistic regression model. Crude odds ratios (COR) with 95% confidence intervals (CI) were calculated in the bivariable analysis. The multivariable model was fitted to assess the association between dependent and independent variables while controlling for potential confounders. Multicollinearity among independent variables was assessed using the variance inflation factor (VIF), with a VIF value <10 indicating the absence of significant multicollinearity. Model fitness was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Adjusted odds ratios (AOR) with 95% CI were used to measure the strength of associations, and variables with a p value <0.05 in the multivariable analysis were considered statistically significant.

Results

Socio-demographic characteristics

A total of 359 asthmatic patients were participated in this study, including 120 cases and 239 controls. Seventy-two (60%) of the cases and 153 (64%) controls were males. The mean age of study participants was (60.25±15.36 standard deviation) for cases and (44.85±11.04 standard deviation) years for controls. Among the study participants, rural resident accounted for 108(90%) of cases and 180(75.3%) of controls (Table 1).

Table 1.

Socio-demographic characteristics of study participants attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables	Category	Pneumonia status
Variables	Category	Pneumonia (+) – n (%)	Pneumonia (-) – n (%)
Sex	Female	48(40)	86(36)
Sex	Male	72(60)	153(64)
Age (in years)	Mean ±SD	60.25±15.365	44.85±11.043
Residence	Urban	12(10)	59(24.7)
Residence	Rural	108(90)	180(75.3)
Religion	Orthodox	117(97.5)	224(93.7)
	Muslim	3(2.5)	14(5.9)
	Protestant	0	1
Education	Unable to read and write	83(69.2)	65(27.2)
	Able to read and write	20(16.7)	71(29.7)
	Primary school	9(7.5)	46(19.2)
	Secondary school	3(2.5)	25(10.5)
	College and above	5(4.2)	32(13.2)
Marital status	Single	5(4.2)	11(4.6)
	Married	98(81.7)	217(90.8)
	Divorced	3(2.5)	7(2.9)
	Widowed	14(11.7)	4(1.7)
Occupation	Farmer	73(60.8)	109(45.6)
	Daily worker	4(3.3)	5(2.1)
	Self-employee	1(0.8)	13(5.4)
	Government employee	5(5.2)	37(15.5)
	House wife	31(25.8)	52(21.8)
	Marchant	3(2.5)	19(7.9)
	Student	3(2.5)	4(1.7)
Household monthly income (ETB)	<2500	54(45)	78(32.6)
	2500-5000	51(42.5)	99(41.4)
	≥5000	15(12.5)	62(25.9)
Household size	<5	53(44.2)	72(30.1)
Household size	≥5	67(55.8)	167(69.9)
Presence of children in the household	No	92(76.7)	128(53.6)
Presence of children in the household	Yes	28(23.3)	111(46.4)

Behavioral and life style related factors

Only two cases have ever smoked and none of the cases are current smokers. Almost all 112(93.3%) of the cases and 202(84.5%) of controls were ever alcohol users. Of these, 91(81.3%) of the cases and 122(60.4%) controls were currently drinking alcohol. Almost more than half, 63(52.5%) of the cases and 169(70.7%) of controls had moderate level of physical activities, and almost all, 114(95%) of the cases and 222(92.9%) of controls had normal weight (Table 2).

Table 2.

Behavioral and life style related factors of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables	Category	Pneumonia status
Variables	Category	Pneumonia (+) – n (%)	Pneumonia (-) – n (%)
Ever smoked tobacco	No	118(98.3)	239(100)
Ever smoked tobacco	Yes	2(1.7)	0
Current tobacco smoking	No	2(100)	0
Current tobacco smoking	Yes	0	0
Ever alcohol use	No	8(6.7)	37(15.5)
Ever alcohol use	Yes	112(93.3)	202(84.5)
Current alcohol use	No	29(24.2)	117(49)
Current alcohol use	Yes	91(75.8)	122(51)
Oral hygiene practice (ever brushed teeth)	No	81(67.5)	56(23.4)
Oral hygiene practice (ever brushed teeth)	Yes	39(32.5)	183(76.6)
Frequency of tooth brushing	Occasionally	35(89.7)	164(89.6)
Frequency of tooth brushing	Frequently	4(10.3)	19(10.4)
Physical activity level	High level	11(9.2)	37(15.5)
	Moderate level	63(52.5)	169(70.7)
	Low level	46(38.3)	33(13.8)
Body mass index	Underweight	4(3.3)	2(0.8)
	Normal weight	114(95)	222(92.9)
	Overweight	2(1.7)	15(6.3)

Medical related factors

About three-fourth 39(32.5%) of the cases and 22(9.2%) of controls had a history of hospital admission in the last one year. They were presented with different medical complains such as tooth and gum disease was the most medical complain among the cases, consisted 24(20%) of cases and five of the controls, whereas, a similar number (nine) of cases and controls had complained of upper respiratory tract infection in the last month. Moreover, the study participants were found with different comorbidities. The most common comorbidities were hypertension consisting 35(29.2%) of cases and five of controls. Similarly, gastric disease, which consisted 13(10.8%) of cases and 12(5.0%) controls, diabetes mellitus accounted eight of cases and one of controls, and only five of cases but none of controls were with cardiovascular disease (Table 3).

Table 3.

Medical related factors of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables	Category	Pneumonia status
Variables	Category	Pneumonia (+) – n (%)	Pneumonia (-) – n (%)
History of hospital admission (past 1 year)	No	81(67.5)	217(90.8)
History of hospital admission (past 1 year)	Yes	39(32.5)	22(9.2)
History of upper respiratory tract infection (past 1 month)	No	111(92.5)	230(96.2)
History of upper respiratory tract infection (past 1 month)	Yes	9(7.5)	9(3.8)
History of tonsillectomy	No	114(95)	236(98.7)
History of tonsillectomy	Yes	6(5)	3(1.3)
History of tooth and gum disease (past 1 month)	No	96(80)	234(97.9)
History of tooth and gum disease (past 1 month)	Yes	24(20)	5(2.1)
History of any type of respiratory tract infection (past 1 month)	No	67(55.8)	216(90.4)
	Yes	53(44.2)	23(9.6)
History of contact with individuals with respiratory infection	No	119(99.2)	238(99.6)
	Yes	1(0.8)	1(0.4)
History of radiographically confirmed pneumonia	No	84(70)	231(96.7)
History of radiographically confirmed pneumonia	Yes	36(30)	8(3.3)
History of diabetes mellitus	No	112(93.3)	238(99.6)
History of diabetes mellitus	Yes	8(6.7)	1(0.4)
History of cardiovascular disease	No	115(95.8)	239(100)
History of cardiovascular disease	Yes	5(4.2)	0
History of gastric disease	No	107(89.2)	227(95)
History of gastric disease	Yes	13(10.8)	12(5)
History of chronic liver disease	No	120(100)	239(100)
History of chronic liver disease	Yes	0	0
History of hypertension	No	85(70.8)	234(97.9)
History of hypertension	Yes	35(29.2)	5(2.1)

Environmental related factors

Majority, 105(87.5%) of the cases and 186(77.8%) of controls had a history of contact with animals. A similar number (six) of the cases and controls had a history of working in a dusty environment. Roughly, all (99.2%) of the cases and 229(95.8%) of controls were used woods as a usual source of cooking fuel (Table 4).

Table 4.

Environmental related factors of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables		Category	Pneumonia status
Variables		Category	Pneumonia (+) – n (%)	Pneumonia (-) – n (%)
History of contact with animals		No	15(12.5)	53(22.2)
History of contact with animals		Yes	105(87.5)	186(77.8)
History of working in dust environment		No	114(95)	233(97.5)
History of working in dust environment		Yes	6(5)	6(2.5)
Household cooking fuel type	Wood	No	1(0.8)	10(4.2)
	Wood	Yes	119(99.2)	229(95.8)
	Charcoal	No	95(79.2)	126(52.7)
	Charcoal	Yes	25(20.8)	113(47.3)
	Electric stove	No	113(94.2)	193(80.8)
	Electric stove	Yes	7(5.8)	46(19.2)

Bronchial asthma related clinical characteristics

About 53(44.2%) of the cases and 212(88.7%) of controls were diagnosed with bronchial asthma lower than 10 years period. Among the study participants, 24(20%) of cases and 70(29.3%) controls had a family history of bronchial asthma, and 94(78.3%) of cases and 27(11.3%) of controls had a history of hospital admission due to acute exacerbation of bronchial asthma. All of the study participants took corticosteroid drugs for the treatment of bronchial asthma, of these 67(55.8%) of cases and 104(43.5%) controls were taking oral corticosteroid. Among study participants, 67(55.8%) of cases and 24(10%) of controls had no regular follow up, and more than three-fourth (79.2%) of the cases and 34(14.2 %) of controls had uncontrolled bronchial asthma (Table 5).

Table 5.

Asthma related clinical characteristics of study participants attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables	Category	Pneumonia status
Variables	Category	Pneumonia (+) – n (%)	Pneumonia (-) – n (%)
Duration since asthma diagnosis	<10 years	53(44.2)	212(88.7)
Duration since asthma diagnosis	≥10 years	67(55.8)	27(11.3)
Family history of asthma	No	96(80)	169(70.7)
Family history of asthma	Yes	24(20)	70(29.3)
History of hospital admission due to acute exacerbation of bronchial asthma (AEBA)	No	26(21.7)	212(88.7)
	Yes	94(78.3)	27(11.3)
Current use of asthma medication	No	0	0
Current use of asthma medication	Yes	120(100)	239(100)
Type of corticosteroid used	Oral corticosteroid	67(55.8)	104(43.5)
Type of corticosteroid used	Inhaled corticosteroid	53(44.2)	135(56.5)
Duration of corticosteroid use	<10 years	53(44.2)	212(88.7)
Duration of corticosteroid use	≥10 years	67(55.8)	27(11.3)
Use of short-acting bronchodilators	No	9(7.5)	37(15.5)
Use of short-acting bronchodilators	Yes	111(92.5)	202(84.5)
Number of salbutamol inhalations per day	<6 inhalations/day	68(61.3)	171(84.7)
Number of salbutamol inhalations per day	≥6 inhalations/day	43(38.7)	31(15.3)
Use of inhalation chamber or spacer	No	105(94.6)	196(97)
Use of inhalation chamber or spacer	Yes	6(5.4)	6(3)
Loss of regular medical follow-up	No	53(44.2)	215(90)
Loss of regular medical follow-up	Yes	67(55.8)	24(10)
Asthma control status	Uncontrolled	95(79.2)	34(14.2)
Asthma control status	Controlled	25(20.8)	205(85.8)

Determinants of pneumonia among adults with bronchial asthma

A binary logistic regression model was employed to assess the association between pneumonia and potential risk factors among adult asthmatic patients. In the bi-variable analysis, several variables were found to be significantly associated with pneumonia at a p-value <0.2, including age, residence, presence of children in the household, ever and current alcohol use, physical activity, tooth brushing habits, history of hospital admission in the past year, history of upper respiratory tract infection in the last month, history of tooth and gum disease in the last month, history of any type of respiratory infection in the last month, previous chest X-ray–confirmed pneumonia, gastric disease, history of hypertension, contact with animals, duration since asthma diagnosis, hospital admission due to AEBA, type of corticosteroid used, use of short-acting bronchodilators, loss of regular medical follow-up, number of salbutamol inhalations per day, and asthma control status.

After adjusting for potential confounders in a multivariable logistic regression analysis, six variables were found to be significantly associated with pneumonia among adult asthmatic patients at a 5% significance level. These included age, current alcohol use, history of hospital admission due to acute exacerbation of bronchial asthma (AEBA) in the past year, type of corticosteroid used, not attending regular medical follow-up appointments, and asthma control status. Each AOR represents the association between a given factor and pneumonia after controlling for the other variables in the multivariable model

The study found that for each additional year of age, the odds of developing pneumonia among adult asthmatic patients increased by 1.06 (AOR = 1.06, 95% CI: 1.01–1.10). Participants who currently use alcohol had 2.93 times higher odds of developing pneumonia compared to those who did not use alcohol (AOR = 2.93, 95% CI: 1.03–4.38). Those with a history of hospital admission due to AEBA had 13.22 times higher odds of developing pneumonia compared to participants without such a history (AOR = 13.22, 95% CI: 9.55–19.51).

Asthmatic patients using inhaled corticosteroids had 4.06 times higher odds of developing pneumonia compared to those taking oral corticosteroids (AOR = 4.06, 95% CI: 3.16 - 7.23). Participants who did not attend regular medical follow-up appointments had 4.48 times higher odds of developing pneumonia than those who maintained regular follow-up (AOR = 4.48, 95% CI: 3.42–7.16). Finally, participants with controlled asthma had 94% lower odds of developing pneumonia compared to those with uncontrolled asthma (AOR = 0.06, 95% CI: 0.02–0.16) (Table 6). The Hosmer-Lemshow goodness of fit test indicated the model was fitted (p = 0.506) and multicollinearity was not a concern as all VIF values were <10.

Table 6.

Bivariable and multivariable binary logistic regression analysis to identify determinants of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone, Northwest Ethiopia, 2025.

Variables	Outcome status		COR (95% CI)	AOR (95% CI)	p-value
Variables	Cases	Controls	COR (95% CI)	AOR (95% CI)	p-value
Age (in years)	60.25±15.37	44.85±11.04	1.095 (1.07 - 1.12)	1.06 (1.01 - 1.10)	0.013*
Residence
Urban	12	59	1	1	-
Rural	108	180	2.95 (1.52–5.73)	4.26 (0.64 - 28.22)	0.133
Presence of children in the household
No	92	128	1	1	-
Yes	28	111	0.35 (0.21–0.57)	1.82 (0.63 - 5.26)	0.267
Ever alcohol use
No	8	37	1	1	-
Yes	112	202	2.56 (1.15–5.71)	3.16 (0.37 - 26.91)	0.294
Current alcohol use
No	29	117	1	1	-
Yes	91	122	3.01 (1.85–4.90)	2.93 (1.03 - 4.38)	0.045*
Oral hygiene practice (ever brushed teeth)
No	81	56	1	1	-
Yes	39	183	0.15 (0.09–0.24)	0.48 (0.16 - 1.42)	0.185
Physical activity level
High level	11	37	1	1	-
Moderate level	63	169	1.25 (0.60–2.61)	0.73 (0.21 - 2.60)	0.632
Low level	46	33	4.69 (2.09–10.52)	1.71 (0.37 - 7.86)	0.489
History of hospital admission (past 1 year)
No	81	217	1	1	-
Yes	39	22	4.75 (2.65–8.50)	0.99 (0.22 - 4.49)	0.994
History of tooth and gum disease (past 1 month)
No	96	234	1	1	-
Yes	24	5	11.70 (4.34–31.56)	3.79 (0.42 - 34.36)	0.236
History of any type of respiratory tract infection (past 1 month)
No	67	216	1	1
Yes	53	23	7.43 (4.24–13.02)	3.02 (0.83 - 11.04)	0.095
History of radiographically confirmed pneumonia
No	84	231	1	1	-
Yes	36	8	12.38 (5.53–27.70)	1.41 (0.20 - 10.21)	0.732
History of gastric disease
No	107	227	1	1	-
Yes	13	12	2.30 (1.01–5.21)	0.26 (0.04 - 1.58)	0.144
History of hypertension
No	85	234	1	1	-
Yes	35	5	19.27 (7.31–50.80)	2.95 (0.45 - 19.45)	0.261
History of contact with animals
No	15	53	1	1	-
Yes	105	186	1.99 (1.07–3.71)	1.50 (0.85–2.65)	0.312
Duration since asthma diagnosis
<10 years	53	212	1	1	-
≥10 years	67	27	9.93 (5.79–17.01)	2.42 (0.63 - 9.40)	0.201
History of hospital admission due to acute exacerbation of bronchial asthma (AEBA)
No	26	212	1	1
Yes	94	27	18.56 (6.72–51.25)	13.22 (9.55 – 19.51)	<0.001*
Type of corticosteroid used
Oral CS	67	104	1	1	-
Inhaled CS	53	135	0.61 (0.39–0.95)	4.06 (3.16 - 7.23)	0.029*
Use of short-acting bronchodilators
No	9	37	1	1	-
Yes	111	202	2.42 (1.21–4.85)	0.66 (0.12, 3.75)	0.638
Number of salbutamol inhalations per day
<6	68	171	1	1	-
≥6	43	31	2.99 (1.49–5.99)	2.64 (0.91 - 7.66)	0.074
Loss of regular medical follow-up
No	53	215	1	1	-
Yes	67	24	11.32 (6.51–19.72)	4.48 (3.42 - 7.16)	0.011*
Asthma control status
Uncontrolled	95	34	1	1	-
Controlled	25	205	0.03 (0.01–0.08)	0.06 (0.02 - 0.16)	<0.001*

*Statistically significant at p-value <0.05; COR = crude odds ratio; AOR = adjusted odds ratio.

Discussion

This study identified the determinants of pneumonia among adult asthmatic patients attending public hospitals in Awi Zone. The findings revealed that older age, current alcohol consumption, a history of hospital admission due to acute exacerbation of bronchial asthma, type of asthmatic medication used, and lack of regular medical follow-up were significant determinants of pneumonia among adults with asthma. In contrast, having well-controlled bronchial asthma was found to have a significant protective effect against pneumonia in this population.

The results of the current study indicate that increasing age was associated with a higher likelihood of developing pneumonia among adult asthmatic patients. This finding is consistent with recent studies from Korea¹⁴ and Spain 1, which reported that asthmatic patients who developed pneumonia were older than those without pneumonia. This association may be explained by age-related changes in physiological and immunological status, leading to decreased immunity against pathogenic bacteria. Additionally, older adults may have increased colonization with Streptococcus pneumoniae, which further elevates the risk of pneumonia.²⁰

The findings of the current study also showed that participants who were currently using alcohol-containing drinks were approximately three times higher odds to develop pneumonia among adult asthmatic patients. Although no previous studies specifically investigated the effect of alcohol consumption on pneumonia among asthmatic patients, this finding is consistent with a systematic review and meta-analysis in the general population²⁵ and a case–control study conducted in Spain ²⁶. The increased risk may be explained by the sedative effect of alcohol, which can elevate the likelihood of aspiration of pathogens from the upper respiratory tract. Additionally, higher levels of alcohol intake can impair alveolar macrophage function, thereby reducing pulmonary defenses against infection.

This study also found that participants with a history of hospital admission due to acute exacerbation of bronchial asthma were 13.25 times higher odds to develop pneumonia compared with those without such a history. This finding is consistent with studies conducted in Korea¹⁴ and the United Kingdom,⁸ which reported that prior hospitalization due to AEBA is a significant risk factor for pneumonia among adult asthmatic patients. This association may be partly explained by increased exposure to pathogens in healthcare settings, as hospitalization elevates the risk of healthcare-associated pneumonia. In addition, asthma exacerbations can accelerate the decline in lung function, impairing the clearance of pathogenic microbes and making individuals more susceptible to bacterial pneumonia.²⁷ Alterations in the lung and gut microbiome may also contribute to this increased risk, as patients with asthma have a higher prevalence of Streptococcus pneumoniae colonization.^27,28 However, the relatively high magnitude of the association should be interpreted cautiously, as residual confounding and unmeasured factors related to asthma severity may still have influenced the observed effect size.

The current study found that inhaled corticosteroid (ICS) use was associated with 4.06 times higher odds of pneumonia compared with oral corticosteroid use among adult asthmatic patients. The finding is novel and should be interpreted cautiously, as there are currently no well-established studies that directly compare the risk of pneumonia between ICS and oral corticosteroid users in asthma populations. Therefore, the observed difference in this study may not reflect a true causal or pharmacological superiority of one treatment over the other, but rather underlying differences in patient characteristics, disease severity, duration of therapy, and treatment indication, which may introduce confounding by indication.

There are studies that reported the increased risk of pneumonia among inhaled corticosteroid users despite not comparing with oral corticosteroid use.^12,14,29 One possible biological explanation is that a large proportion of inhaled corticosteroid particles are deposited in the oropharynx and subsequently swallowed, which may increase exposure of the upper airway to colonized oral bacteria.³⁰ Aspiration of oropharyngeal secretions into the lower respiratory tract is a recognized pathway for the development of pneumonia, suggesting a potential indirect mechanism through which inhaled corticosteroids may contribute to respiratory infection risk.³¹ In addition, chronic airway diseases such as asthma have been associated with alterations in airway microbiota, suggesting that disruption of normal respiratory microbial balance may contribute to increased susceptibility to bacterial respiratory infections in these patients.³² However, these mechanisms should be considered as general biological plausibility for pneumonia risk in asthma rather than specific explanations for differences between inhaled and oral corticosteroid use.

This study also revealed that individuals who did not attend their scheduled regular follow-up during their appointments had 4.48 times higher odds to have pneumonia than those who attend their regular follow-up appointments. However, national studies exploring the association of loss of regular medical follow-up appointment with pneumonia among asthmatic patients are scarce. This significant association in this study might be due to that attending and following scheduled medical follow-up helps patients to control their asthma with the help of healthcare professionals.

Additionally, the findings of the current study revealed that participants with controlled bronchial asthma had 94% lower odds of developing pneumonia compared with those who had uncontrolled asthma. This result is consistent with studies conducted in the United States³³ and Denmark.⁴ The observed association may be explained by the fact that patients with well-controlled asthma exhibit more effective phagocytic pathways and an enhanced phagocytic response toward bacterial airway pathogens, which improves bacterial clearance from the lung microenvironment.³⁴ Furthermore, well-controlled asthma is associated with less functional alteration of lung tissue, thereby reducing susceptibility to bacterial infections such as pneumonia.²⁹

The findings of this study have important clinical implications for the management of adult asthmatic patients. Particular attention should be given to older adults, patients with a history of alcohol consumption, previous hospital admission due to asthma exacerbation, and those with poor adherence to regular follow-up care, as these groups were found to have increased risk of pneumonia. Strengthening routine follow-up care, improving asthma control, promoting adherence to prescribed treatment, and providing counseling on modifiable behavioral factors such as alcohol consumption may help reduce the occurrence of pneumonia among asthmatic patients. In addition, healthcare professionals should closely monitor patients receiving inhaled corticosteroids and reinforce proper inhaler techniques to minimize potential respiratory complications.

Strengths and limitations

This study has some limitations that should be considered. First, the case-control design limits the ability to establish causal relationships. Second, as the study was hospital based, the findings may not be generalizable to the broader community. Third, there is potential for selection bias, as cases and controls were enrolled consecutively until the required sample size was reached, which may lead to overrepresentation of patients who more frequently attend follow-up care or have differing disease severity compared with the source population. Recall bias may also have affected the results, particularly among controls, as cases may recall exposures more accurately. In addition, social desirability bias could have influenced responses to sensitive variables such as alcohol consumption, physical activity, smoking status, and oral hygiene practices. Furthermore, the relatively strong association observed between prior hospital admission due to acute exacerbation of bronchial asthma and pneumonia may be influenced by residual confounding and unmeasured clinical factors, particularly asthma severity, treatment adherence, and overall disease control, which were not fully accounted for in the analysis.

Despite these limitations, this study has several strengths. It is the first case-control study examining the determinants of pneumonia among adult asthmatic patients in low-income countries, providing valuable hypothesis-generating data. The study relied on primary data and included only radiologically confirmed pneumonia cases among patients with asthma, excluding individuals with a known history of chronic obstructive pulmonary disease (COPD), which strengthens the validity of the findings. Furthermore, the study was also conducted in multi-centers which increase the generalizability of the finding.

Conclusion

This study identified age, current alcohol use, prior hospital admission due to acute exacerbation of bronchial asthma, use of inhaled corticosteroids, lack of regular medical follow-up, and asthma control as significant determinants of pneumonia among adult asthmatic patients. Older age, alcohol intake, and previous hospitalizations increased the risk, while controlled asthma and regular follow-up were protective. Although the role of inhaled corticosteroids remains debated, our findings suggest their use may increase pneumonia risk, highlighting the need for careful monitoring and individualized management. To reduce pneumonia risk, healthcare systems should strengthen public awareness, optimize asthma control programs, and promote regular follow-up, while healthcare professionals should educate patients on modifiable risk factors, ensure optimal asthma management, carefully weigh the benefits and risks of inhaled corticosteroid use, and minimize unnecessary hospital admissions. Future multicenter, and community-based studies are recommended to establish causal relationships, assess dose-dependent effects of inhaled corticosteroids, and improve generalizability through comprehensive clinical, behavioral, and environmental assessments.

Supplemental material

Supplemental material - Determinants of pneumonia among adult asthmatic patients attending public hospitals in awi zone, northwest Ethiopia: A case control study

Supplemental material for Determinants of pneumonia among adult asthmatic patients attending public hospitals in awi zone, northwest Ethiopia: A case control study by Abiyie Bitew Godie, Daniel Mulat Eshetu, Wolde Melese Ayele, Sileshi Berihun, Mikias Getahun Molla in Sage Open Medicine

Footnotes

Acknowledgments

We would like to thank public hospitals in Awi zone for their cooperation in granting access to necessary information, and to the study participants, data collectors, and supervisors for their full collaboration and support during the data collection process. We also express our deepest gratitude to the Amhara Public Health Institute for providing an official approval letter to conduct this study.

ORCID iD

Daniel Mulat Eshetu

Ethical considerations

Ethical approval for this study was obtained from the Institutional Research Ethics Review Committee of Injibara University (Ref No. IU/IRERC/30/25). Formal permission to conduct the study was also obtained from the Amhara Public Health Institute (APHI) and the administrators of hospitals prior to data collection. The study was conducted in accordance with the principles of the Declaration of Helsinki. Only information relevant to the study objectives was collected, and participants were not identified by name or any personal identifiers.

Consent to participate

Written informed consent was obtained from all study participants prior to data collection. For participants unable to read or write, the consent information was read aloud and thumbprint consent was obtained in the presence of an impartial witness.

Authors’ Contributions

Abiyie Bitew Godie and Daniel Mulat Eshetu conceived and designed the study and supervised all study activities, including data management, analysis, and interpretation. Wolde Melese Ayele, Sileshi Berihun, and Mikias Getahun Molla contributed to data management, analysis, and interpretation. All authors participated in drafting and revising the manuscript and approved the final version for publication.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.*

Supplemental material

Supplemental material for this article is available online.

Appendix

References

Terraneo

Polverino

Cilloniz

, et al. Severity and outcomes of community acquired pneumonia in asthmatic patients. Respiratory Medicine 2014; 108(11): 1713–1722. https://doi.org/10.1016/j.rmed.2014.09.001

Negash

Tsegabrhan

Meles

, et al. Determinants of Acute Asthma Attack among adult asthmatic patients visiting hospitals of Tigray, Ethiopia, 2019: case control study. Asthma research and practice 2020; 6(1): 1. https://doi.org/10.1186/s40733-020-00054-w

Megersa

Chala

Fikremariam

. Determinants of asthma attack among adult asthmatic patients attending at Public Hospitals of West Shoa Zone, Oromia Regional State, Ethiopia, 2021: case–control study. Journal of Asthma and Allergy 2022; 15: 1143–1154. https://doi.org/10.2147/JAA.S376499

Kassaw

Mohammed

Tessema

, et al. Outcomes and predictors of severe community-acquired pneumonia among adults admitted to the University of Gondar comprehensive specialized hospital: a prospective follow-up study. Infection and drug resistance 2023; 16: 619–635. https://doi.org/10.2147/IDR.S392844

Torres

Cilloniz

Niederman

, et al. Pneumonia Nat Rev Dis Primers 2021; 7: 25. https://doi.org/10.1038/s41572-021-00259-0

Almirall

Serra-Prat

Bolíbar

, et al. Risk factors for community-acquired pneumonia in adults: a systematic review of observational studies. Respiration 2017; 94(3): 299–311. https://doi.org/10.1159/000479089

Cabanes

Valentín

Moragón

. Pneumonia in asthma patients: are we giving it enough attention? Archivos de bronconeumologia 2019; 55(7): 397–398. https://doi.org/10.1016/j.arbres.2018.12.013

Zaidi

Blakey

. Why are people with asthma susceptible to pneumonia? A review of factors related to upper airway bacteria. Respirology 2019; 24(5): 423–430. https://doi.org/10.1111/resp.13528

Pelton

Shea

Bornheimer

, et al. Pneumonia in young adults with asthma: impact on subsequent asthma exacerbations. Journal of asthma and allergy 2019; 12: 95–99. https://doi.org/10.2147/JAA.S200492

10.

Kahsay

Gebru

Gahse

. Risk factors of community acquired pneumonia among adults in Tigray, Ethiopia: a case-control study. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH 2018; 12(5): LG01–LG05. https://doi.org/10.7860/jcdr/2018/31150.11506

11.

Dupuis

Sabra

Patrier

, et al. Burden of pneumococcal pneumonia requiring ICU admission in France: 1-year prognosis, resources use, and costs. Critical Care 2021; 25(1): 24. https://doi.org/10.1186/s13054-020-03442-z

12.

Qian

Coulombe

Suissa

, et al. Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi‐cohort study. British journal of clinical pharmacology 2017; 83(9): 2077–2086. https://doi.org/10.1111/bcp.13295

13.

Kwak

Choung

Park

, The association between asthma and invasive pneumococcal disease: a nationwide study in Korea. Journal of Korean medical science 2015; 30(1): 60–65. https://doi.org/10.3346/jkms.2015.30.1.60

14.

Kim

M-H

Rhee

Shim

J-S

, et al. Inhaled corticosteroids in asthma and the risk of pneumonia. Allergy, Asthma & Immunology Research 2019; 11(6): 795–805. https://doi.org/10.4168/aair.2019.11.6.795

15.

Osman

Ahmed

ElSony

. Factors associated with uncontrolled asthma among Sudanese adult patients. Journal of the Pan African Thoracic Society 2021; 2(2): 85–93. https://doi.org/10.25259/jpats_22_2020

16.

Mulugeta

Tesfahun

Mamo

, et al. Determinants of Community-Acquired Pneumonia Among Adults Patients Attending Debre Berhan University Hakim Gizaw Hospital, Northeast Ethiopia: A Case–Control Study. International Journal of General Medicine 2023; 16: 5271–5279. https://doi.org/10.2147/IJGM.S434954

17.

Fida

Kaba

Worku

. Alcohol use and its associated factors among Ethiopian military personnel. BMJ Mil Health 2024; 170(4): 320–324. https://doi.org/10.1136/military-2022-002217

18.

Kenore

Abrha

Yosef

, et al. Determinants of hypertension among patients with diabetes mellitus in public hospitals of Kembata Tambaro Zone, South nations nationalities and peoples region, Ethiopia, 2021; A case control study. Journal of Multidisciplinary Healthcare 2022; 15: 2141–2152. https://doi.org/10.2147/JMDH.S379293

19.

Forde

. Scoring the international physical activity questionnaire (IPAQ). University of Dublin, 2018, vol 3.

20.

Mekuria

Seyoum

Ataro

, et al. Prevalence, Antimicrobial Resistance, and Associated Factors of Streptococcus pneumoniae Colonization Rate among Old‐Age Patients with Respiratory Tract Infection Attending Sheik Hassan Yebere Referral and Karamara General Hospitals, Jigjiga, Ethiopia. Canadian Journal of Infectious Diseases and Medical Microbiology 2022; 2022(1): 9338251. https://doi.org/10.1155/2022/9338251

21.

Geleta

Dadi

Sona

. Determinants of uncontrolled asthma among adult asthmatic patients on follow-up at chest clinic of Jimma medical center: unmatched case-control study. Journal of Asthma 2022; 59(6): 1103–1109. https://doi.org/10.1080/02770903.2021.1908351

22.

Gebresillasie

Worku

Ahmed

, et al. Determinants of asthma among adults in Tigray, Northern Ethiopia: a facility-based case-control study. PeerJ 2024; 12: e16530. https://doi.org/10.7717/peerj.16530

23.

Heluf

Assefa

Dessie

, et al. Factors associated with uncontrolled asthma among adult asthmatic patients in eastern Ethiopia: A multicenter study, SAGE Open Med 2022;10:20503121221132165. https://doi.org/10.1177/20503121221132165

24.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61(4): 344–349. https://doi.org/10.1016/j.jclinepi.2007.11.008

25.

Simou

Britton

Leonardi-Bee

, Alcohol and the risk of pneumonia: a systematic review and meta-analysis. BMJ open 2018; 8(8): e022344. https://doi.org/10.1136/bmjopen-2018-022344

26.

Fernández-Solá

Junqué

Estruch

, et al. High alcohol intake as a risk and prognostic factor for community-acquired pneumonia. Archives of Internal medicine 1995; 155(15): 1649–1654. https://doi.org/10.1001/archinte.1995.00430150137014

27.

Lee

Park

Y-B

. Inhaled corticosteroids is not associated with the risk of pneumonia in asthma. Tuberculosis and Respiratory Diseases 2023; 86(3): 151–157. https://doi.org/10.4046/trd.2022.0147

28.

Rodríguez

Duran

Muñoz

, et al. Oral health and risk of pneumonia in asthmatic patients with inhaled treatment. Medicina Clínica (English Edition) 2018; 150(12): 455–459. https://doi.org/10.1016/j.medcli.2017.07.024

29.

Ekbom

Quint

Schöler

, et al. Asthma and treatment with inhaled corticosteroids: associations with hospitalisations with pneumonia. BMC Pulmonary Medicine 2019; 19(1): 254. https://doi.org/10.1186/s12890-019-1025-1

30.

X-O

D’Urzo

. A review on the safety and efficacy of inhaled corticosteroids in the management of asthma. Pulmonary Therapy 2017; 3(1): 1–18. https://doi.org/10.1007/s41030-017-0043-5

31.

Marik

. Aspiration pneumonitis and aspiration pneumonia. New England Journal of Medicine 2001; 344(9): 665–671. https://doi.org/10.1056/NEJM200103013440908

32.

Uzer

Karaboğa

Çalış

, et al. Microbial variations in sputum cultures among hospitalized patients with community-acquired pneumonia: differences in sputum microbiota between asthma and COPD patients. Jornal Brasileiro de Pneumologia 2024; 50(2): e20230329. https://doi.org/10.36416/1806-3756/e20230329

33.

Donnelly

Barnes

. Defective phagocytosis in airways disease. Chest 2012; 141(4): 1055–1062. https://doi.org/10.1378/chest.11-2348

34.

Hough

Curtiss

Blain

, et al. Airway remodeling in asthma. Frontiers in medicine 2020; 7: 191. https://doi.org/10.3389/fmed.2020.00191

35.

Shrestha

C-I

Liu

, et al. Risk of pneumonia in asthmatic children using inhaled corticosteroids: a nested case-control study in a birth cohort. BMJ open 2022; 12(3): e051926. https://doi.org/10.1136/bmjopen-2021-051926

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