We defined a case as a person with influenza-like illness admitted (for a minimum of an overnight stay) to a Sydney metropolitan hospital from July 1 through August 31, 2009, who had laboratory confirmation of pandemic (H1N1) 2009 by PCR that was notified to the Department of Health. Patients <16 years of age or residing outside metropolitan Sydney were excluded from the study because we assumed the threshold for hospital admission may have been different for this age group and for patients in regional and rural areas. To ensure complete case ascertainment, all cases notified in the study period were cross-matched with the Department of Health database containing all hospital admissions in NSW for the study period; additional identified cases were included in the study. If case-patients were not able to complete a telephone interview because of ill health or disability, another household member completed the interview on their behalf. Up to 30 attempts were made to contact case-patients by telephone.

In a case–control study, we compared demographic and health information reported by case-patients with those of controls. We defined a control as a person >16 years of age residing in metropolitan Sydney who had not been hospitalized for influenza in 2009. Telephone numbers (stratified by AHS) were used to randomly select potential control households. Within each AHS in Sydney, we selected 2 households per case. A single control was randomly selected from within each selected household for interview. Up to 12 attempts were made to contact selected households. Fewer attempts were made to contact controls than case-patients as a result of random-digit generation methods described in detail elsewhere (24). The age and sex distribution of participating controls was compared with that of the metropolitan Sydney population.

We used a standard questionnaire to ask case-patients and controls about influenza symptoms, pregnancy or delivery within the previous 28 days, weight and height, smoking history, current and previous medications, and past hospitalizations. In addition, information was collected regarding diagnosis of general health conditions, including asthma, lung disease (defined as emphysema, chronic lung problems and/or chronic bronchitis), heart disease (defined as heart problems from birth, rheumatic heart disease, angina, heart attack, and/or heart failure excluding hypertension), diabetes (type I or II), other metabolic disorders, kidney disease (defined as kidney transplant, renal failure, and/or dialysis), liver disease, blood disorders (defined as sickle cell disease, thalassemia, or hemoglobin problems), mental health diagnoses, neurologic conditions (defined as conditions that involve muscles, nerves, or the brain), immune suppression (defined as cancer, HIV infection, or immunosuppressive medication), and obstructive sleep apnea. Ethics approval was not required because information was collected under NSW Public Health Act 1991 (21)

In univariate analysis, the proportions of characteristics among case-patients and controls were compared by using χ² tests. In multivariate analysis, independent risk factors for hospitalization were assessed through logistic regression by using backward elimination. All variables with a univariate level of significance p<0.25 were selected for inclusion in the base model, and variables were excluded if the p value was >0.05 and did not meaningfully alter the point estimates of the remaining variables. Because a similar proportion of case-patients and controls reported a diagnosis of asthma not requiring regular medication, only a history of asthma requiring regular medication was included in the final logistic regression model.

Additional logistic regression models were constructed to compare case-patients with controls for women of child-bearing age (16–45 years), case-patients who received mechanical ventilation compared with all controls, case-patients who sought medical attention within 48 hours of onset of symptoms compared with case-patients who sought medical attention after 48 hours, and controls who reported symptoms of influenza-like illness during the study period (defined as self-reported fever and either cough or sore throat) with controls who reported no illness during the study period. Mechanical ventilation (rather than intensive care unit admission) was used as a measure of severity of illness because cases were reported from several hospital facilities with varying criteria for patient admission to intensive care. The model fit the data well by the Hosmer-Lemeshow goodness-of-fit test (χ² = 15.85, 9 df, p = 0.07). Seventy-nine percent of pairs were concordant, and c = 0.804.

The median age of case-patients was 45 years (range 16–88 years). Of the 302 case-patients, 125 (41%) were male, 68 (23%) were admitted to a high dependency or intensive care unit, and 37 (12%) required mechanical ventilation. The median length of hospital stay was 4 nights (range 1–91 nights). Reported risk factors among case-patients included a history of asthma (38%, including 29% who required regular medication), lung disease (19%), diabetes (19%), mental health diagnosis (18%), heart disease (14%), pregnancy (13%), obstructive sleep apnea (12%), immune suppression (10%), neurologic condition (8%), liver disease (8%), kidney disease (3%), blood disorders (5%), and metabolic conditions (1%) (Table A1).

None of the case-patients reported giving birth in 28 days before symptom onset. Of the 40 patients who were pregnant at the time of symptom onset, 28 (70%) were in their third trimester. Sixty-six (22%) case-patients were current smokers, and 91 (30%) were ex-smokers. Among the 91 ex-smokers, the median time smoked was 20 years (range 1–60 years, median 15 cigarettes/day); 39 reported cessation >5 years prior to illness, 15 patients between 12 months and 5 years, and 37 patients within the past 12 months. Among the 66 current smokers, the median time smoked was 20 years (range 1–60 years; median 10 cigarettes/day) (online Appendix Table).

There were no significant differences in characteristics of case-patients and controls by place of residence, receipt of 2009 seasonal influenza vaccination, or history of neurologic disorders (Table A1). In univariate analysis, compared with controls, case-patients were more likely to be male, aged 16–35 years and 46–55 years, have higher body mass index (BMI), and report a history of asthma, heart disease, mental health diagnosis, immune suppression, obstructive sleep apnea, lung disease, diabetes, liver disease, blood disorder, and pregnancy, and smoking (Table A1).

In the logistic regression model, age, sex, asthma (requiring regular medication), smoking (current or ex-smoker), heart disease, immune suppression, lung disease, diabetes, and pregnancy were independently associated with hospitalization for pandemic (H1N1) 2009 (Table 1). Similar results were found when analysis was restricted to men only or women only. The factor most strongly associated with hospitalization was pregnancy, followed by lung disease, immune suppression, and ages 16–25 and 46–55 years (Table 1). Overall, 262 (86%) case-patients reported >1 independent risk factor (asthma, heart disease, immune suppression, lung disease, diabetes, pregnancy, or smoking) compared with 315 (52%) of controls (p<0.0001). The risk for hospitalization increased with increasing number of reported significant risk factors.

In the logistic regression model for women of childbearing age, asthma (requiring regular medication), lung disease, diabetes, and pregnancy were independently associated with hospitalization for pandemic (H1N1) 2009 (Table 2). In total, 88% of women of childbearing age hospitalized for pandemic (H1N1) 2009 reported 1 of the risk factors compared with 39% of controls (p <0.0001). Pregnancy was the only risk factor reported for 25% of hospitalized women of childbearing age.

In univariate analysis, compared with controls, case-patients who required mechanical ventilation were more likely to report a history of lung disease, asthma (requiring regular medication), have a higher BMI, be pregnant, have an influenza vaccination in the previous 12 months, and be 26–45 years of age (Table 3). In the logistic regression model for ventilated case-patients, a history of lung disease, diabetes, pregnancy, high BMI, or status as a current or ex-smoker were independently associated with mechanical ventilation (Table 3).

Of the 603 controls, 113 (19%) reported an influenza-like-illness during the study period. There was no significant difference in underlying risk factors between controls who reported influenza-like-illness and controls who did not report any respiratory symptoms. However, influenza-like-illness was significantly more common among controls aged 16–25 (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.4–7.5, p = 0.005) and 36–45 years (OR 3.0, CI 1.4–6.2, p = 0.004) compared with controls aged >65 years.

Information on the time from onset of illness to medical attention was available for 295 (98%) case-patients. Of these, 238 (81%) reported having >1 risk factor listed in the public message campaigns. Overall, the proportion of case-patients seeking medical attention was similar for both those with reported risk factors and those with no risk factors (80% and 79%, respectively). There was no significant difference in individual underlying risk factors between case-patients who sought medical attention within 48 hours of symptoms and those who did not (Table 4).