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Morbid Obesity=20 as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic = Influenza=20 A(H1N1) Disease

Severe illness due to 2009 pandemic A(H1N1) infection has been = reported among=20 persons who are obese or morbidly obese. We assessed whether obesity is = a risk=20 factor for hospitalization and death due to 2009 pandemic influenza = A(H1N1),=20 independent of chronic medical conditions considered by the Advisory = Committee=20 on Immunization Practices (ACIP) to increase the risk of = influenza-related=20 complications.

We used a case-cohort design to compare cases of hospitalizations and = deaths=20 from 2009 pandemic A(H1N1) influenza occurring between = April=E2=80=93July, 2009, with a=20 cohort of the U.S. population estimated from the 2003=E2=80=932006 = National Health and=20 Nutrition Examination Survey (NHANES); pregnant women and children <2 = years=20 old were excluded. For hospitalizations, we defined categories of = relative=20 weight by body mass index (BMI, kg/m²); for deaths, obesity = or morbid=20 obesity was recorded on medical charts, and death certificates. Odds = ratio (OR)=20 of being in each BMI category was determined; normal weight was the = reference=20 category. Overall, 361 hospitalizations and 233 deaths included = information to=20 determine BMI category and presence of ACIP-recognized medical = conditions. Among=20 =E2=89=A520 year olds, hospitalization was associated with being = morbidly obese (BMI=E2=89=A540)=20 for individuals with ACIP-recognized chronic conditions = (OR=E2=80=8A=3D=E2=80=8A4.9, 95% CI=20 2.4=E2=80=939.9) and without ACIP-recognized chronic conditions = (OR=E2=80=8A=3D=E2=80=8A4.7, 95%CI=20 1.3=E2=80=9317.2). Among 2=E2=80=9319 year olds, hospitalization was = associated with being=20 underweight (BMI=E2=89=A45^th percentile) among those with = (OR=E2=80=8A=3D=E2=80=8A12.5, 95%CI=20 3.4=E2=80=9345.5) and without (OR=E2=80=8A=3D=E2=80=8A5.5, 95%CI = 1.3=E2=80=9322.5) ACIP-recognized chronic=20 conditions. Death was not associated with BMI category among individuals = 2=E2=80=9319=20 years old. Among individuals aged =E2=89=A520 years without = ACIP-recognized chronic=20 medical conditions death was associated with obesity = (OR=E2=80=8A=3D=E2=80=8A3.1, 95%CI: 1.5=E2=80=936.6)=20 and morbid obesity (OR=E2=80=8A=3D=E2=80=8A7.6, 95%CI = 2.1=E2=80=9327.9).

Our findings support observations that morbid obesity may be = associated with=20 hospitalization and possibly death due to 2009 pandemic H1N1 infection. = These=20 complications could be prevented by early antiviral therapy and=20 vaccination.

Article=20

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Oliver W. Morgan¹,=20 Anna=20 Bramley²,=20 Ashley=20 Fowlkes²,=20 David S.=20 Freedman³,=20 Thomas H.=20 Taylor⁴,=20 Paul=20 Gargiullo²,=20 Brook=20 Belay³,=20 Seema=20 Jain²,=20 Chad = Cox²,=20 Laurie=20 Kamimoto²,=20 Anthony=20 Fiore²,=20 Lyn=20 Finelli²,=20 Sonja J.=20 Olsen¹,=20 Alicia M.=20 Fry²^*

1 Division of Emerging Infections and=20 Surveillance Services, Centers for Disease Control and Prevention, = Atlanta,=20 Georgia, United States of America, 2=20 Influenza Division, Centers for Disease Control and Prevention, Atlanta, = Georgia, United States of America, 3=20 Division of Nutrition and Physical Activity and Obesity, Centers for = Disease=20 Control and Prevention, Atlanta, Georgia, United States of America, 4 Division of Bacterial Diseases, = Centers for=20 Disease Control and Prevention, Atlanta, Georgia, United States of = America

Abstract Top

Background
Severe=20 illness due to 2009 pandemic A(H1N1) infection has been reported among = persons=20 who are obese or morbidly obese. We assessed whether obesity is a risk = factor=20 for hospitalization and death due to 2009 pandemic influenza A(H1N1),=20 independent of chronic medical conditions considered by the Advisory = Committee=20 on Immunization Practices (ACIP) to increase the risk of = influenza-related=20 complications.

Methodology/Principal Findings
We=20 used a case-cohort design to compare cases of hospitalizations and = deaths from=20 2009 pandemic A(H1N1) influenza occurring between April=E2=80=93July, = 2009, with a=20 cohort of the U.S. population estimated from the 2003=E2=80=932006 = National Health and=20 Nutrition Examination Survey (NHANES); pregnant women and children <2 = years=20 old were excluded. For hospitalizations, we defined categories of = relative=20 weight by body mass index (BMI, kg/m²); for deaths, obesity = or morbid=20 obesity was recorded on medical charts, and death certificates. Odds = ratio (OR)=20 of being in each BMI category was determined; normal weight was the = reference=20 category. Overall, 361 hospitalizations and 233 deaths included = information to=20 determine BMI category and presence of ACIP-recognized medical = conditions. Among=20 =E2=89=A520 year olds, hospitalization was associated with being = morbidly obese (BMI=E2=89=A540)=20 for individuals with ACIP-recognized chronic conditions (OR =3D 4.9, 95% = CI=20 2.4=E2=80=939.9) and without ACIP-recognized chronic conditions (OR =3D = 4.7, 95%CI=20 1.3=E2=80=9317.2). Among 2=E2=80=9319 year olds, hospitalization was = associated with being=20 underweight (BMI=E2=89=A45^th percentile) among those with (OR = =3D 12.5, 95%CI=20 3.4=E2=80=9345.5) and without (OR =3D 5.5, 95%CI 1.3=E2=80=9322.5) = ACIP-recognized chronic=20 conditions. Death was not associated with BMI category among individuals = 2=E2=80=9319=20 years old. Among individuals aged =E2=89=A520 years without = ACIP-recognized chronic=20 medical conditions death was associated with obesity (OR =3D 3.1, 95%CI: = 1.5=E2=80=936.6)=20 and morbid obesity (OR =3D 7.6, 95%CI 2.1=E2=80=9327.9).

Conclusions/Significance
Our=20 findings support observations that morbid obesity may be associated with = hospitalization and possibly death due to 2009 pandemic H1N1 infection. = These=20 complications could be prevented by early antiviral therapy and=20 vaccination.

Citation: Morgan OW, Bramley A, Fowlkes A, Freedman = DS,=20 Taylor TH, et al. (2010) Morbid Obesity as a Risk Factor for = Hospitalization and=20 Death Due to 2009 Pandemic Influenza A(H1N1) Disease. PLoS ONE 5(3): = e9694.=20 doi:10.1371/journal.pone.0009694

Editor: Thorkild I. A. Sorensen, Institute of = Preventive=20 Medicine, Denmark

Received: December 11, 2009; = Accepted:=20 February 24, 2010; Published: March 15, 2010

This is an open-access article distributed under the terms of the = Creative=20 Commons Public Domain declaration which stipulates that, once placed in = the=20 public domain, this work may be freely reproduced, distributed, = transmitted,=20 modified, built upon, or otherwise used by anyone for any lawful = purpose.

Funding: The authors have no support or funding to=20 report.

Competing interests: The authors have declared that = no=20 competing interests exist.

* E-mail: afry@cdc.gov

Introduction Top

Since April 2009, = the 2009=20 pandemic influenza A(H1N1) virus, a novel influenza virus with a = combination of=20 gene segments not previously reported in swine or human influenza = viruses, has=20 spread worldwide and caused epidemics of disease. [1],=20 [2]=20 Early reports suggest that persons with chronic medical conditions = previously=20 recognized as increasing the risk for complications due to seasonal = influenza=20 also have a higher risk of complications due to 2009 pandemic influenza = A(H1N1)=20 infection. [3],=20 [4]=20 Consequently, the Advisory Committee on Immunization Practices (ACIP) = included=20 individuals with these recognized chronic medical conditions in their = priority=20 groups for receipt of the new 2009 pandemic influenza A(H1N1) vaccine. = [5]

Preliminary data = from the=20 United States and abroad suggest that obesity (body mass index, = BMI=E2=89=A530=20 kg/m²) and morbid obesity (BMI=E2=89=A540 kg/m²) = is=20 disproportionately represented among hospitalizations, intensive care=20 admissions, and deaths from 2009 pandemic influenza A(H1N1). [6],=20 [7],=20 [8],=20 [9]=20 We explored the hypothesis that BMI is a risk factor for hospitalization = and=20 death due to pandemic influenza A(H1N1), independent of ACIP-recognized = chronic=20 medical conditions.

Methods Top

We used three = datasets:=20 patients hospitalized with 2009 pandemic influenza A(H1N1), deaths from = 2009=20 pandemic influenza A(H1N1), and the National Health and Nutrition = Examination=20 Survey (NHANES), a representative survey of the general U.S. population. = For=20 each dataset we defined individuals according to BMI category (see = below),=20 presence of ACIP-recognized chronic medical conditions (defined for this = analysis as cardiovascular disease, pulmonary disease, liver disease, = cancer,=20 and diabetes) and age group. We did not include neurologic, = neuromuscular,=20 hematological, non-diabetes metabolic disorders or immunosuppression as=20 ACIP-recognized chronic medical conditions in this analysis due to lack = of this=20 information from NHANES. We used two age groups, 2=E2=80=9319 years and = =E2=89=A520 years:=20 dividing the =E2=89=A520 year old age group into additional age = categories resulted in=20 unreliable variance estimates when we stratified by BMI category and = presence of=20 ACIP-recognized chronic medical conditions due to zero observations in = primary=20 sampling units of the NHANES survey.

For hospitalized = patients and=20 NHANES participants we used BMI [height (m)/weight (kg)²] as = an index=20 of relative weight. For individuals aged 2=E2=80=9319 years, we = calculated age- and=20 sex-specific BMI z-scores and used CDC 2000 growth charts to define BMI=20 category, where underweight was <5^th percentile, normal = weight=20 5=E2=80=9384^th percentile, overweight = 85=E2=80=9394^th percentile, and=20 obese was =E2=89=A595^th percentile. [10],=20 [11],=20 [12]=20 For individuals =E2=89=A520 years we defined underweight as BMI<18.5, = normal weight=20 as 18.5=E2=80=9324.9, overweight as 25.0=E2=80=9329.9, obese as = 30.0=E2=80=9339.9, and morbidly obese=20 =E2=89=A540.0. [13],=20 [14]=20 For deaths, no data were available on measured height and weight, so we = used=20 mention of obesity or morbid obesity within the medical condition = section of the=20 reporting form. For all three datasets we excluded individuals <2 = years old=20 and pregnant women because obesity definitions are not applicable to = them.

We included = information on=20 516 (10%) of 5009 patients hospitalized with 2009 pandemic influenza = A(H1N1) in=20 the United States between May 1=E2=80=93July 12, 2009. These patients = were a convenience=20 sample of all hospitalizations reported to CDC from 24 states as part of = prospective surveillance project, as described previously, [15]=20 for which state health departments abstracted information from medical = charts=20 using a standard case form. We were provided with additional reports of=20 hospitalizations from New York City, Wisconsin, and Texas, that were not = included in the surveillance project, but had been collected by health=20 departments using the same or similar abstraction forms during the same = time=20 period. If height and weight were not reported in data collected for the = prospective study, we attempted to contact patients for this = information. For a=20 minority of patients for whom we had weight but not height data, we = estimated=20 their obesity category by assuming that their height was not less than = the=20 5^th percentile or greater than the 95^th percentile = of the=20 population (see Supplement=20 S1). We included information on deaths reported to CDC from April 27 = to July=20 23, 2009. State health departments collected information from medical = charts,=20 medical examiner reports, and death certificates, using a standard data=20 collection form. All hospitalizations and deaths included in our = analyses were=20 confirmed to have pandemic H1N1 infection by real-time reverse = transcription=20 polymerase chain reaction (rRT-PCR). [16]=20 We estimated the proportion of the U.S. population in different BMI = categories=20 from NHANES 2003=E2=80=934 and 2005=E2=80=936. NHANES methodology has = been described previously.=20 [17]

For each dataset, = we=20 calculated the proportion of individuals in each BMI category by age = group (2=E2=80=9319=20 years and =E2=89=A520 years). We stratified our analysis by presence or = absence of an=20 ACIP-recognized chronic medical condition, which is likely to confound = the=20 relationship between BMI category and hospitalization or death due to = 2009=20 pandemic A(H1N1) influenza. We calculated the ratio of odds (odds ratio, = OR) of=20 being in each BMI category, where the normal weight category was the = reference=20 category, for hospitalizations and deaths (cases) compared to the U.S.=20 population (cohort). Because we compared cases to the cohort of the U.S. = population selected before the time period during which cases could = occur (i.e.,=20 a case-cohort design), the OR estimates the risk ratio of = hospitalization or=20 death by BMI category. [18]=20 To estimate 95% confidence intervals (95%CI) and p-values of the odds = ratios we=20 used the Taylor series linearization method to combine the variance = estimate of=20 the log-odds of exposure among cases (hospitalizations or deaths) with a = variance of the log-odds of exposure among the population as estimated = using=20 NHANES. [19],=20 [20]=20 For hospitalized patients, we conducted a sensitivity analysis to = consider how=20 robust our analysis was with regard to adjustment of age among = =E2=89=A520 year olds, by=20 creating a logistic regression model for each BMI category with Normal = weight as=20 the reference category, where hospitalization was the dependent variable = and age=20 group (20.0=E2=80=9335.4, 35.5=E2=80=9345.9, 46.0=E2=80=9354.9, = =E2=89=A555.0 years) was the independent=20 variable (see Supplement=20 S1). We conducted a further sensitivity analysis of our treatment of = missing=20 BMI data (see Supplement=20 S1). We also repeated the analysis for hospitalized patients after = changing=20 the comparison group to a cohort of the U.S. population that had been = admitted=20 to hospital for any reason in a 12 month period, as estimated by NHANES. = The=20 rationale for this additional analysis was to assess whether any = observed=20 association between BMI category and hospitalization was due to more = frequent=20 hospitalization among obese and morbidly obese individuals. We used SAS = 9.2 for=20 all analyses.

The investigation = of 2009=20 pandemic influenza A(H1N1) infections was deemed public health = surveillance, not=20 human subjects research and therefore did not require Institutional = Review Board=20 review.

Results Top

Between April and = July 2009,=20 we identified 565 hospitalized patients with confirmed 2009 pandemic = H1N1=20 infection; we excluded 51 patients who were pregnant and 77 who were = <2 years=20 old. Of the remaining 437 patients, 283 (65%) had both measured height = and=20 weight which we used to calculate BMI. In addition, we estimated BMI = category=20 for 78 (19%) patients who had data on measured weight but not measured = height;=20 52 (27%, n =3D 52/191) were patients aged 2=E2=80=9319 years, of which = 19% were estimated=20 to be underweight and 23% were estimated to be obese; 26 (11%, n =3D = 26/246) were=20 patients =E2=89=A520 years, of which 42% were estimated to be obese or = morbidly obese.=20 Our final hospitalized cohort included 361 patients assigned to a BMI=20 category.

There were 304 = deaths among=20 persons with 2009 pandemic influenza A(H1N1) reported to CDC; 16 = pregnant women=20 and eight children <2 years old were excluded. Of the remaining 280 = deaths,=20 10 (4%) were missing data about chronic medical conditions and 37 (13%) = about=20 obesity, leaving 233 deaths in our analysis: 31 were 2=E2=80=9319 years = old and 202 were=20 =E2=89=A520 years old.

In the U.S. = population aged=20 2=E2=80=9319 years, the prevalence of ACIP-recognized chronic medical = conditions=20 increased with increasing BMI category: 16.4% were obese and 20.7% had=20 ACIP-recognized chronic medical conditions (Table=20 1). In comparison, among hospitalized patients 2=E2=80=9319 years = old, 25.5% were=20 obese, of whom 53.7% had ACIP-recognized chronic medical conditions. = Among=20 deaths in 2=E2=80=9319 year olds, 9.7% were obese, of whom 33.3% had = ACIP-recognized=20 chronic medical conditions. In the US population =E2=89=A520 years old, = 28.0% were obese=20 and 5.4% were morbidly obese; the prevalence of ACIP-recognized chronic = medical=20 conditions increased only slightly with increasing BMI category: 40.9% = of obese=20 and 51.2% of morbidly obese persons had ACIP-recognized chronic medical=20 conditions. Among hospitalized patients with 2009 pandemic H1N1 = infection =E2=89=A520=20 years old, 32.5% were obese and 67.7% of these obese patients had=20 ACIP-recognized chronic medical conditions, while 22.5% were morbidly = obese, of=20 whom 77.8% had ACIP-recognized chronic medical conditions. Among deaths = in =E2=89=A520=20 year olds, 38.1% were obese and 12.4% were morbidly obese; = ACIP-recognized=20 chronic medical conditions were reported for 63.6% of deaths among obese = and=20 56.0% of morbidly obese individuals.

Table= 1.=20 Number=20 and percent of persons with ACIP-recognized chronic underlying medical=20 conditions, by category of body mass index = (BMI).
doi:10.1371/journal.pone.0009694.t001

Among patients = 2=E2=80=9319 years,=20 there was no statistically significant association between being = overweight or=20 obese and hospitalization among those who did or did not have = ACIP-recognized=20 chronic medical conditions (Table=20 2). However, being underweight was associated with hospitalization = among=20 patients 2=E2=80=9319 years old with and without ACIP-recognized chronic = medical=20 conditions (OR =3D 12.5, 95%CI 3.4 to 45.5, p<0.001; OR =3D 5.5, = 95%CI 1.3 to=20 22.5, p<0.001, respectively) (Table=20 2). There was no association between BMI category and death among = persons=20 2=E2=80=9319 years old (Table=20 2).

Table= 2.=20 Odds=20 Ratio of BMI category for patients hospitalized or deaths with 2009 = pandemic=20 influenza A(H1N1) compared to the U.S. population, by category of body = mass=20 index (BMI) and presence of ACIP-recognized chronic medical = conditions^*.
doi:10.1371/journal.pone.0009694.t002

Among hospitalized = patients=20 aged =E2=89=A520 years with and without ACIP-recognized chronic medical = conditions,=20 morbid obesity was the only BMI category statistically associated with=20 hospitalization (OR =3D 4.9, 95%CI 2.4 to 9.9, p<0.001; OR =3D 4.7, = 95%CI 1.3 to=20 17.2, p<0.001, respectively). These associations remained after = adjustment=20 for age (Supplement=20 S1 Table S3), when we excluded patients with measured weight but no = measured=20 height (Supplement=20 S1 Table S1) and when we assumed that all persons with missing = height and=20 weight were in the normal weight category (Supplement=20 S1 Table S2). However, the association between morbid obesity and=20 hospitalization among individuals who did not have an ACIP-recognized = chronic=20 medical condition was not statistically significant in the final = sensitivity=20 analysis (Supplement=20 S1 Table S2).

BMI category was = not=20 associated with death among adults who had an ACIP-recognized chronic = medical=20 condition. However, death was associated with obesity and morbid obesity = among=20 adults who did not have an ACIP-recognized chronic medical condition (OR = =3D 3.1,=20 95%CI 1.5 to 6.6, p<0.001; OR =3D 7.6, 95%CI 2.1 to 27.9, p<0.001, = respectively) (Table=20 2).

When we repeated = our analysis=20 using the subgroup of the U.S. population that had been hospitalized in = the=20 previous year as the comparison group, morbid obesity remained = associated with=20 hospitalization among =E2=89=A520 year olds with ACIP-recognized chronic = medical=20 condition (OR =3D 4.1, 95%CI 2.0 to 8.7, p<0.001), but not = significantly so for=20 patients with no ACIP-recognized chronic medical condition (OR =3D 4.2, = 95%CI 1.0=20 to 18.0, p =3D 0.1) (Table=20 3).

Table= 3.=20 Odds=20 Ratio of BMI category for patients hospitalized with 2009 pandemic = influenza=20 A(H1N1) compared to the U.S. NHANES 2003=E2=80=932006 population = hospitalized for any=20 reason over a 12-month period, by category of body mass index (BMI) and = presence=20 of ACIP-recognized chronic medical conditions.
doi:10.1371/journal.pone.0009694.t003

Discussion Top

Our analysis of = early data=20 from the 2009 pandemic in the United States suggests that morbid = obesity, but=20 not obesity, was statistically associated with hospitalization from 2009 = pandemic H1N1 influenza among adults both who do and do not have chronic = medical=20 conditions. These findings are consistent with reports from surveillance = data of=20 a high prevalence of morbid obesity among patients hospitalized with = 2009=20 pandemic H1N1 influenza. [6],=20 [7],=20 [8],=20 [9].=20 Among 2=E2=80=9319 year olds, hospitalization was associated with being = underweight,=20 irrespective of presence of ACIP-recognized chronic medical conditions = evaluated=20 in this analysis. Additionally, we found that deaths among =E2=89=A520 = year olds without=20 ACIP-recognized chronic medical conditions were more likely to be obese = or=20 morbidly obese individuals.

Previous studies = have=20 demonstrated that obesity was associated with an increased number of all = cause=20 hospitalization in adults, [21]=20 although there is no information about the role of obesity in severe = disease due=20 to seasonal influenza. In our study, the elevated risk for = hospitalization due=20 to 2009 pandemic H1N1 infection persisted even when we restricted our = analysis=20 to the U.S. population that reported at least one hospitalization in the = previous year, suggesting that the observed associations were not = because=20 morbidly obese persons routinely experience higher hospitalization = rates.=20 Several studies indicate that morbid obesity may plausibly be an = independent=20 risk factor for complications due to 2009 pandemic H1N1 disease: morbid = obesity=20 is associated with complications in the intensive care unit, including = prolonged=20 stay, prolonged ventilation, and death [22],=20 [23]=20 and women with BMI=E2=89=A530 have a higher likelihood of developing = community acquired=20 pneumonia. [24]=20 The risk for hospitalization among persons =E2=89=A520 years of age with = morbid obesity=20 was similar regardless of the presence of ACIP-recognized chronic = medical=20 conditions, suggesting that the effect of morbid obesity is independent = of the=20 presence of ACIP-recognized chronic medical conditions.

We expected to see = similar=20 associations between deaths and BMI categories that we saw for = hospitalizations.=20 That we did not see the same association, especially for obesity and for = persons=20 with ACIP-recognized risk factors, may reflect (1) misclassification of = BMI=20 categories among deaths which did not have measured BMI or (2) = incomplete=20 reporting of ACIP-recognized chronic medical conditions. Due to the = possible=20 misclassification of both BMI and underlying conditions among fatalities = these=20 results should be interpreted with caution. Additional studies are = necessary to=20 better define the risk of BMI category and underlying conditions, and = death due=20 to 2009 pandemic H1N1 infection.

Children aged = 2=E2=80=9319 years who=20 were obese had an elevated, but not statistically significant, risk of=20 hospitalization due to 2009 pandemic H1N1 infection and no increased = risk of=20 death. However, the number of pediatric deaths and hospitalizations were = small=20 and confidence intervals were wide. In addition, children aged = 2=E2=80=9319 years who=20 were underweight had an elevated significant risk of hospitalization due = to 2009=20 pandemic H1N1 infection. Among the hospitalized children in the = underweight BMI=20 category, 20% (n =3D 3/15) had neuromuscular/neurodevelopment disorders = and 13% (n=20 =3D 2/15) had immunosuppressive conditions. For this analysis, none of = these=20 conditions were included as an ACIP-recognized risk group due to lack of = similar=20 data from NHANES. Therefore, inclusion of these children in our analysis = may in=20 part be responsible for the observation of an increased risk of = hospitalization=20 among underweight children. The collection of additional data over time = may give=20 further insight into the risk of BMI category and hospitalization or = death due=20 to 2009 pandemic H1N1 infection among children.

This analysis of = data=20 collected during the first wave of the 2009 pandemic H1N1 epidemic in = the United=20 States was exploratory and findings should be considered preliminary = until=20 results from larger and more comprehensive studies are available. There = are a=20 number of potential limitations of our analysis. Even though our data = about=20 hospitalized patients and deaths were convenience samples, they were = collected=20 before the first reports were published suggesting that obesity may be=20 associated with severe pandemic H1N1 disease. [4]=20 We used data from NHANES from 2003=E2=80=932006 to estimate obesity in = the U.S.=20 population, which has remained constant over the last few years and so = is likely=20 to reflect the prevalence of obesity in 2009 [25].=20 Moreover, the high response rates for NHANES (the proportion of sampled=20 individuals who were interviewed and had a physical examination was 76% = in=20 2003=E2=80=934 and 77% in 2005=E2=80=936) indicate that = obesity-dependent selection bias is=20 unlikely. An advantage of NHANES is that the height and weight of = respondents is=20 measured. Medical conditions were self-reported and could have been = under- or=20 over-reported. It is hard to determine the extent to which this could = have=20 introduced systematic bias. Moreover, NHANES does not collect = information about=20 immunosuppression and neurologic/neuromuscular and hematological = conditions. [5]=20 To reduce the possibility of bias in our comparison, we did not include = these=20 conditions in our definition of ACIP-recognized chronic medical = conditions for=20 hospitalized patients or deaths. This is likely to have resulted in an=20 underestimation of the prevalence of chronic medical conditions in all = of the=20 data sources included in our analysis. While height and weight were = incompletely=20 recorded for hospitalized patients, our results were robust to various=20 assumptions about these missing data and we conclude that the observed=20 associations with morbid obesity were unlikely to be due to missing data = bias.=20 However, we had no height or weight data for deaths, and our results of = the=20 association between BMI category and death should be interpreted with = caution.=20 Finally, some of the observed effect may be due to residual confounding = by=20 race/ethnicity, which we could not adjust for due to incomplete data for = both=20 hospitalizations and deaths. The impact of this potential bias cannot be = determined from our data. Differences in obesity prevalence have been = observed=20 only between non-Hispanic black and Mexican-American women but not = between other=20 racial/ethnic groups or among men. [26]

Our findings = suggest that in=20 the United States persons who are morbidly obese, even if they do not = have=20 chronic medical conditions recognized by ACIP as increasing the risk of=20 influenza-related complications, may be at increased risk for = hospitalization=20 and potentially also for death due to 2009 pandemic H1N1 infection. = However,=20 additional studies with a larger sample of patients and appropriate = comparison=20 groups are needed to confirm these findings. We found that at least half = of=20 Americans who are morbidly obese reported other ACIP-recognized medical=20 conditions and it is possible that some persons who are morbidly obese = also have=20 unrecognized chronic medical conditions. Clinicians should evaluate = morbidly=20 obese patients with possible influenza illness for the presence of = chronic=20 medical conditions and if these conditions are present, or if persons = with=20 morbid obesity show signs of lower respiratory tract infection or other = signs of=20 severe illness, these patients should receive empiric antiviral = treatment as=20 early as possible. [27]=20 In addition, as vaccine becomes available these persons will likely = benefit from=20 vaccination with the 2009 H1N1 vaccine.

Supporting Information Top

Supplement=20 S1.
Morbid=20 Obesity as a Risk Factor for Hospitalization and Death due to 2009 = Pandemic=20 Influenza A(H1N1) Disease.
(0.11=20 MB DOC)

Acknowledgments Top

We thank New York = City 2009=20 Swine Flu Investigation team, Laura Tabony at the Texas Department of = State=20 Health Services and Wisconsin Department of Health for sharing = hospitalization=20 data. We are grateful to Elizabeth Zell and Dr. Timothy Uyeki from the = Centers=20 for Disease Control and Prevention for their advice about analyzing = these=20 data.

Data Access and=20 Responsibility: Alicia M Fry and Oliver Morgan had full access to = all the=20 data in the study and takes responsibility for the integrity of the data = and the=20 accuracy of the data analysis.

Disclaimer: = The=20 findings and conclusions in this report are those of the authors and do = not=20 necessarily represent the views of the Centers for Disease Control and=20 Prevention.

Author Contributions Top

Conceived and = designed the=20 experiments: OWM PG BB LK AF LF SO AMF. Performed the experiments: OWM = THT.=20 Analyzed the data: OWM AB AF DSF THT PG SO AMF. Contributed=20 reagents/materials/analysis tools: OWM AB AF DSF THT PG SJ CC AMF. Wrote = the=20 paper: OWM DSF PG BB SJ LK AF LF SO AMF.

References Top

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Morbid Obesity=20 as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic = Influenza=20 A(H1N1) Disease

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