Among a national case-series of patients hospitalized with pH1N1 infection in the U.S., during both waves of the pH1N1 pandemic, almost one in every three patients hospitalized with pH1N1 virus infection two years or older had asthma. The majority of hospitalized persons with asthma and pH1N1 infection had an uncomplicated hospital course with less pneumonia upon admission, need for mechanical ventilation and death in this group compared with those without asthma. However, almost 40% of the patients hospitalized with pH1N1 infection with asthma had pneumonia upon admission, and these patients were more likely to require ICU admission or die than patients with asthma who did not have pneumonia upon admission. Data from this analysis suggest that early treatment with influenza antiviral agents within 2 days of admission may be beneficial in reducing illness severity in patients with asthma.
In our analysis, the proportion of children (35%) and adults (26%) with asthma who were hospitalized with pH1N1 infection was notably higher than the national prevalence of asthma among children (9.6%) and adults (7.7%) in the U.S. [17
]. These data are consistent with both seasonal and pandemic influenza U.S. reports demonstrating similar proportions of asthma among patients hospitalized with influenza. From 2005–2008, among adults (n
1267) hospitalized with seasonal influenza, 27% of adults aged 18–49 years had asthma [6
]. In a recent national multi-center study that included 2,165 children aged 2–17 years old hospitalized with influenza from 2003 to 2009, 32% had asthma, with a higher proportion (44%) during the 2009 pH1N1 pandemic compared with previous seasons [18
]. Data from international studies reported similar proportions of asthma among hospitalized patients with pH1N1 infection including reports from Australia (31%), Ireland (18%), Singapore (19%), Spain (23%), and the United Kingdom (25%) [10
In our age group stratified analysis, patients with asthma were more likely to have COPD than patients without asthma. As over 20% of the patients in our case-series were 50 years or older and there is an overlap in asthma and COPD obstructive pathophysiology in the airways [19
], this is not an unexpected finding. As persons with asthma age, the airway obstruction becomes less reversible due to airway remodeling from chronic inflammation and fibrosis leading to a more chronic obstructive pathology that retains features of asthma [20
]. The elderly may have asthma alone, COPD alone, or both; diagnosing either asthma or COPD alone may be challenging, in part because these patients may not be regularly monitored with spirometry to document progression of their obstructive disease [21
]. In addition, almost 60% of patients with asthma and COPD were current smokers, which likely contributed to their dual co-morbidities.
Approximately 30% of patients with and without asthma in our analysis were admitted to the ICU, but overall the majority of patients with asthma had an uncomplicated hospital course, including less mechanical ventilation and death compared with those without asthma. The reasons for this are unclear. Patients included in our analysis may have been admitted to an ICU more readily if they had a history of asthma as a precaution and not due to the severity of their present illness; this would bias our analysis to demonstrating less severe outcomes in this group. Other reports which also used chart review to determine presence of asthma have reported similar findings. In a recent national multi-center study that included 1,434 children aged 2–17 years old with asthma who were hospitalized with seasonal and pandemic influenza from 2003 to 2009, 14–24% were admitted to the ICU but only 2–11% had respiratory failure and
1% of these patients required extracorporeal membrane oxygenation or died [18
]. In a California pH1N1 case-series that included 1,088 adults and children, 24% of patients had asthma but fewer deaths occurred in those with asthma than those without asthma (7% versus 12%) [9
]. In a global pooled analysis of patients hospitalized with pH1N1 infection that included asthma data from 11 countries, while asthma was the most common underlying condition associated with hospitalization, a higher proportion of patients with asthma survived compared with patients with other conditions [15
]. When looking at country specific data, this also holds true, including in one of the largest studied cohorts in the United Kingdom where asthma was the most common underlying condition among 1520 hospitalized pH1N1 patients but had a significant lower odds of death [22
Patients with asthma in our analysis were also less likely to have a diagnosis of pneumonia upon admission than patients without asthma. Our study results are in contrast with a recent national multi-center study of 2,992 children under 18 years old hospitalized with seasonal influenza from 2003 to 2008 who had a chest radiograph performed, in which patients with asthma were more likely than those without asthma to have pneumonia (41% versus 34%, p
]. This study differed from our analysis in the following ways: it examined seasonal not pandemic influenza, included only children, and permitted the chest radiograph to be performed anytime during hospitalization as opposed to at admission as is used for our analysis. These study design differences could help explain the different findings between these two studies. However, it is important to note that in both studies, almost 40% of patients with asthma had pneumonia. Pneumonia is a known complication of influenza [24
] and is an important cause of morbidity during seasonal and pandemic influenza periods [5
]. Further clarity on the relationship between asthma and influenza-associated pneumonia is needed to better understand which persons with asthma are at greater risk for pneumonia.
The majority of patients in our analysis received influenza antiviral agents with no significant differences among those with and without asthma, including in relation to illness onset or admission time; in addition there was no significant difference in time from illness onset to admission between the two groups. However, only 50% of patients with asthma received antiviral agents within 2 days of illness onset. It is unclear if delayed treatment was due to delay in testing, delayed ascertainment of results, or antiviral agent clinical prescribing practice. When looking at factors associated with ICU admission or death, early antiviral treatment in relation to hospital admission was found to be protective among those with asthma. This adds to the existing evidence underscoring the importance of early influenza treatment among those persons with suspected or confirmed influenza infection who are hospitalized and those with underlying medical conditions, including asthma, regardless of their prior vaccination status as is recommended by the Advisory Committee on Immunization Practices (ACIP) [26
Our data are subject to limitations. The patients described in this analysis were derived from two hospitalization case-series that used different sampling methods [7
]. However, data from both periods were nationally representative of hospitalizations from areas in the U. S. where peak disease activity was occurring at the time. Patients included in this analysis were confirmed for pH1N1 virus and may not be representative of hospitalized patients who may not have been tested. Despite use of a standard data collection form, not all information was collected for all patients, including influenza vaccination status (pH1N1 vaccine was not readily available during the study); this limits our ability to assess these interventions, however the study was not designed to address these specific questions. In addition diagnoses of asthma and ARDS were ascertained from history and clinical diagnosis and not by a standardized clinical assessment. We were also not able to determine the level of baseline severity of asthma among patients described in this cases-series, including past hospitalizations, intubations, and steroid or inhaler use, which could help explain which persons with asthma are at risk for more severe outcomes. Patients with asthma may have been misclassified as having COPD or vice versa.