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(Chest. 2001;119:115-119.)
© 2001 American College of Chest Physicians

Influence of Gender on Rates of Hospitalization, Hospital Course, and Hypercapnea in High-Risk Patients Admitted for Asthma*

A 10-year Retrospective Study at Yale-New Haven Hospital

David R. Trawick, MD, PhD; Carole Holm, RN and Joel Wirth, MD, FCCP

* From the Pulmonary and Critical Care Medicine Unit (Dr. Trawick), University of Rochester Medical Center, Rochester, NY; the Section of Pulmonary and Critical Care Medicine (Ms. Holm), Yale University School of Medicine, New Haven, CT; and the Division of Pulmonary and Critical Care Medicine (Dr. Wirth), Maine Medical Center, Portland, ME. From the Pulmonary and Critical Care Medicine Unit (Dr. Trawick), University of Rochester Medical Center, Rochester, NY; the Section of Pulmonary and Critical Care Medicine (Ms. Holm), Yale University School of Medicine, New Haven, CT; and the Division of Pulmonary and Critical Care Medicine (Dr. Wirth), Maine Medical Center, Portland, ME.

Correspondence to: David R. Trawick, MD, PhD, Universityof Rochester Medical Center, 601 Elmwood Ave, Box 692, Rochester, NY 14642-8677; e-mail: David_Trawick{at}URMC Rochester.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To compare the relative numbers and hospital course of men vs women admitted at least twice with asthma or status asthmaticus to Yale-New Haven Hospital (YNHH) during the period from 1985 to 1994.

Design: A retrospective chart review.

Setting: YNHH.

Patients: High-risk men and women (age range, 18 to 50 years) admitted at least twice during the study period with the discharge diagnosis of asthma or status asthmaticus.

Results: Of 561 adult asthma patients admitted during the study period, 188 were admitted at least twice and accounted for 68% of the total asthma admissions. One hundred three of the 188 patients were randomly selected, and all of their asthma admissions were retrospectively reviewed. The 103 patients accounted for 382 admissions. Seventy-two percent of these patients and 68.6% of the admissions were women. The proportions of each gender requiring admission to the medical ICU (15.65% women vs 11.67% men) or intubation (8.00% women vs 5.80% men) were not significantly different. Women did exhibit a definite trend toward longer admissions (4.92 days vs 4.04 days; p < 0.554). A significantly higher proportion of female patient admissions underwent initial arterial blood gas analysis than men (56.9% vs 44.2%; p < 0.05). Factorial analysis demonstrated a highly significant main effect of gender on PCO2 levels (p < 0.0001). Men, overall, had higher PCO2 levels than women (48.73 mm Hg vs 41.04 mm Hg; p < 0.036). Male patients admitted to the medical ICU or requiring intubation had significantly higher PCO2 levels than their respective female counterparts (p < 0.05).

Conclusions: At YNHH, 68% of all admissions for asthma in this age group are attributable to high-risk patients. High-risk female patients are admitted twice as often as high-risk male patients and tend to have longer admissions. Once admitted, however, the proportion of men and women requiring the medical MICU or intubation were similar. High-risk male patients on presentation are consistently more hypercapneic than high-risk female patients. Therefore, the mechanisms contributing to the gender differences in asthma admissions may include differences in the ventilatory response to hypercapnea or in the tolerance to airway obstruction.

Key Words: asthma • gender • high-risk asthma • hospitalization • hypercapnea • near-fatal asthma • severity


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Although gender and age influence the expression of numerous diseases,1 their effect on the incidence or expression of asthma is not clear. While the overall annual age-adjusted hospital discharge rate for asthma in female patients from 5 to 34 years of age is consistently higher than that of similarly aged male patients,2 asthma admissions for male patients from 0 to 10 years of age are nearly twice that of age-equivalent female patients. After age 20 years, female asthma patient admissions again predominate, occurring at a rate approximately 2.5 times that of their male counterparts.3 This crossover in asthma admission rates appears to occur during or very soon after adolescence and remains relatively constant thereafter. The mechanisms accounting for this crossover are unknown.

In 1995, we developed a database, the purpose of which was to understand better the demographics and epidemiology of high-risk adult asthmatic patients admitted to Yale-New Haven Hospital (YNHH) from 1985 to 1994. We defined high-risk individuals as patients from 18 to 50 years of age with at least two admissions for asthma or status asthmaticus during the study interval. As the database grew, a predominance in female patient admissions became evident. These data initially suggested to us that high-risk female patients might experience a more severe form of asthma than high-risk male patients, resulting in more admissions. If this hypothesis were true, then one may expect a more protracted or more complicated hospital course. To test our hypothesis, we used this database to determine to what degree high-risk adult female patients were admitted in excess of their male counterparts. We then retrospectively reviewed a sample of all the admissions to determine whether high-risk female patients experienced longer hospitalizations, more hospitalizations per individual, more frequent intensive care admissions, more intubations, a longer duration of intubation, and a greater degree of hypercapnea on presentation than their high-risk male counterparts.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Design
The study was conducted at YNHH, an urban, tertiary-care teaching hospital. The computerized medical record database of the hospital was used to identify patients admitted with the following characteristics: (1) primary diagnosis of asthma or status asthmaticus; (2) age 18 to 50 years; (3) at least two admissions for asthma or status asthmaticus during the study period of January 1, 1985, to December 31, 1994.

A total of 188 patients were identified who met these criteria. One hundred seven of the 188 patients were randomly selected, and the medical records of each admission for asthma or status asthmaticus experienced by the patient during that 10-year period were reviewed. Four of the 107 patients were excluded after chart review revealed coding errors. Data extracted from each admission included, but was not limited to, the following: age on admission, duration of admission, floor to which the patient was originally admitted, initial arterial blood gas (ABG) measures (when obtained), and the need for and duration of intubation. These and other data were entered into a statistical and graphics spreadsheet for analysis (JMP; SAS Institute; Cary, NC).

Statistics
Analysis of categorical variables was performed using the {chi}2 test. Analysis of continuous variables was performed using analysis of variance. The Tukey-Kramer HSD (honestly significant difference) test was used in assessing differences in multiple comparisons. Factorial analysis was employed to assess for main and interactive effects.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Five hundred sixty-one patients (age range, 18 to 50 years) were admitted to YNHH for asthma or status asthmaticus during the 1985 to 1994 period, accounting for 1,151 admissions. Of these 561 patients, 188 patients (33.5%) were admitted at least twice, accounting for 778 admissions or 68% of the total. One hundred seven of these 188 patients were randomly selected for retrospective chart review of each of their admissions for asthma. Four patients were excluded after chart review.

The 103 patients accounted for 382 admissions. Seventy-five of 103 patients (72.8%) and 262 of 382 admissions (68.6%) were women (Tables 1 , 2). {chi}2 analysis demonstrated that the distribution of race between genders was not significantly different among patients or admissions (Tables 1 , 2) . Female patient admissions were significantly older than male patient admissions. However, no significant difference existed between the number of admissions per man or woman (Table 2) . The maximum number of repeat admissions for men was 23 and for women was 12. Women did demonstrate a definite trend toward longer admissions (Table 2) .


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  		Table 1.. Patient Characteristics*

 

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  		Table 2.. Admission Characteristics*

 
Fifty-five of 382 patients (14.4% of all admissions) required care in the medical ICU (MICU), and 28 of 382 patients (7.3%) underwent intubation (Table 3 ). Although fewer men were admitted than women, the proportion of men requiring intensive care was not significantly different from that of women (Table 3) . Of the 55 patients admitted to the MICU, 28 patients required intubation and mechanical ventilation. Again, although the absolute number of women entering the MICU was higher than that of men, the proportion of each gender requiring intubation was not significantly different (Table 3) . Furthermore, there was no significant difference in the duration of intubation between men and women (Table 3) .


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  		Table 3.. Hospital Course*

 
Two hundred two of 382 patients (52.9% of all admissions) underwent ABG analysis as part of their initial evaluation. A significantly higher proportion of female patient admissions underwent initial ABG analysis than male patient admissions (56.9% vs 44.2%; p < 0.05).

Men, overall, exhibited significantly higher PCO2 levels than women (p < 0.0036; Fig 1 ). Men admitted to the floor tended to have higher levels of PCO2 (p < 0.05 by t test but not by the Tukey-Kramer HSD (honestly significant difference) test; Fig 1 ) than women admitted to the floor. Men admitted to the MICU exhibited significantly higher PCO2 levels than female counterparts (p < 0.05; Fig 1 ). Likewise, intubated men had significantly higher PCO2 levels than intubated women (p < 0.05; Fig 1 ). Factorial analysis demonstrated significant main effects of gender (p < 0.0001), location (p < 0.0001), and intubation status (p < 0.0001) on PCO2 levels (Fig 1) .



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  		Figure 1.. Comparison of PCO2 levels in women vs men. For all admissions, there were 149 women and 53 men; for floor admissions, there were 108 women and 41 men; for MICU admissions, there were 42 women and 11 men; for intubated patients, there were 21 women and 6 men. Statistically different adjacent data sets are denoted by ** (p < 0.05). Data are expressed ± SEM. Gender, location to which the patient was admitted, and intubation status all respectively affected PCO2 levels at a high level of significance (p < 0.01; see text).

 
Two deaths occurred (one woman and one man) in the 382 admissions. Both experienced sudden attacks and were intubated in the field. Both experienced severe anoxic encephalopathy.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The significant findings of our study were as follows: (1) at YNHH, approximately one third of the patients admitted for asthma during the study were high-risk patients who accounted for two thirds of all the asthma admissions; (2) greater than two thirds of all high-risk asthma admissions were women; (3) high-risk female patients tended to have a longer length of stay than high-risk male patients; (4) once admitted, the proportion of high-risk women and high-risk men requiring admission to the MICU or intubation were similar; (5) high-risk male patients were significantly more hypercapneic on presentation than high-risk female patients; and (6) a significantly higher proportion of high-risk female patients were subjected to ABG analysis than high-risk male patients.

The cost of illness related to asthma in 1990 is estimated to be $6.2 billion.4 Inpatient hospital services represent the largest single direct medical expenditure, approaching $1.6 billion.4 In our database, we chose to examine high-risk patients since they have, essentially by definition, an increased risk for repeat hospitalization.5 Furthermore, virtually all of our patients met criteria for potentially fatal asthma,6 which would predispose them to substantial morbidity and expectantly high health-care resource utilization. To our knowledge, this is the first study to demonstrate the proportion of asthma hospital admissions attributable to high-risk patients. Future studies examining the characteristics of high-risk asthma patients may assist primary intervention strategies to reduce asthma morbidity, hospitalizations, and mortality.

The higher number of female patient asthma admissions relative to male patients initially suggested to us that high-risk female patients might be experiencing a more severe form of asthma. To the contrary, although high-risk women outnumbered high-risk men by two to one at YNHH, once admitted to the hospital the two groups experienced comparable hospital courses. The proportion of high-risk women requiring MICU care, intubation, and length of intubation was not significantly different from men. Furthermore, no significant difference was noted in the number of admissions per patient between men and women over the 10-year period. Of note, women did tend to have longer admissions than men by almost an entire day. Although women were slightly but significantly older than their male counterparts and increased age is associated with increased length of stay in asthma hospitalizations,3 the age difference is small. Moreover, Skobeloff et al3 demonstrated a statistically significant difference in length of hospital stay between age-identical men and women hospitalized for asthma after 31 years of age. Whether the increased length of stay reflects gender-related differences is asthma severity is not known.

In general, the admission rates for all medical-surgical diagnoses nationwide reflect a female-to-male predominance (60% vs 40%, respectively), which is similar to the female-to-male proportions in asthma admissions seen in our study and nationwide.7 This observation suggests that the gender differences in asthma admissions may be no different than any other disease. However, two studies3 8 demonstrated that the prevalence of wheeze and asthma hospitalizations, respectively, exhibit a male predominance before and a female predominance after adolescence. That this crossover occurs during or very soon after adolescence raises the possibility of hormonal modulation of asthma9 10 11 12 13 by an undetermined mechanism. Gender-specific differences exist in airway hyperreactivity,14 which are manifested during adolescence.15 However, no change in airway responsiveness is detectable during the natural menstrual cycle or in asthmatic women taking oral contraceptives.16

Other factors contributing to gender differences in asthma admissions may include preferential exposure of women to environmental triggers such as viruses, chemical irritants, and aeroallergens.17 Supporting the latter is an investigation18 demonstrating a higher degree of atopy in female asthmatics relative to men.

Our study suggests that gender-specific differences in the ventilatory response to airflow obstruction or to hypercapnea may contribute, at least in part, to the gender-related differences in asthma hospitalizations. Hypercapnea in acute asthma is associated with severe airflow obstruction.19 Asthma patients presenting with hypercapnea often have a longer duration of chronic asthma, and are more likely to be steroid dependent and to have pulsus paradoxus than are nonhypercapneic patients.20 We therefore considered PCO2 a gauge of the severity of the acute exacerbation and to reflect some of the chronic features of the illness in the patient. The reason high-risk male patients are more hypercapneic than high-risk female patients in our study is unknown. Mountain and Sahn20 reported similar findings. For a given resistive load, men can generate greater maximal inspiratory pressure and maximal expiratory pressure.21 Perhaps because of this gender differential in maximal inspiratory and expiratory pressures, women are more symptomatic than men at lower resistive loads, prompting clinicians to obtain ABG measures earlier and/or more frequently during the evaluation of an asthma exacerbation. Supporting this theory is the observation in the present study that proportionally more female patients underwent ABG analysis on admission than male patients.

Another possibility is that the ventilatory response to PCO2 in high-risk men is diminished relative to that of high-risk women. The ventilatory response to progressive hyperoxic hypercapnea is significantly attenuated in patients with near-fatal asthma.22 Whether this decreased chemosensitivity also exhibits gender differences is not known. Gender differences in chemosensitivity, in general, are suggested by the male predominance in chronic hypercapneic states, such as obesity-hypoventilation syndrome and by the induction of a Pickwickian syndrome after testosterone administration.20 Conversely, in women, augmentation of hypercapneic chemosensitivity occurs during the luteal phase, when progesterone levels are 30-fold that of the follicular phase of the menstrual cycle.23

Our study is biased by the fact the data were generated by patients who experienced multiple hospitalizations for asthma. Therefore, extrapolation of our results to asthma patients who have never been hospitalized may be unwarranted. Furthermore, YNHH is situated in an urban setting with demographics that do not reflect the United States as a whole. Because both asthma hospitalizations and mortality rates are significantly influenced by race and/or socioeconomic factors, it was important to demonstrate that proportionally equal representation of races existed across gender (Table 1) .2 24

In summary, our study demonstrates that high-risk patients account for the majority of asthma admissions at YNHH and that high-risk female patient admissions outnumber high-risk male patient admissions by two to one. Most intriguing was the observation that high-risk men in our study were significantly more hypercapneic than high-risk women despite no difference in MICU or intubation rates. The mechanisms contributing to the gender differences in asthma admissions may include differences in the ventilatory response to hypercapnea or in the tolerance to airway obstruction and are deserved of further study.


   Footnotes
 
Abbreviations: ABG = arterial blood gas; MICU = medical ICU; YNHH = Yale-New Haven Hospital

Received for publication November 9, 1999. Accepted for publication August 28, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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