INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

To date, there is little agreement as to what extent personality profiles and behavioral aspects of patients may influence asthma. Though previous studies suggested that emotional factors were important influences in asthma (1, 2), later reports could not demonstrate any differences in the mental health between asthmatic and nonasthmatic subjects (3, 4). Indeed, coping with a chronic disease such as asthma is greatly influenced not only by the features of the disease but also by the personality and behavioral characteristics of the patient (5). Thus, psychological factors, such as stress and anxiety, can influence and be affected by the clinical changes of asthma severity (6). In fact, patients with "brittle" asthma have greater psychiatric morbidity than those with less severe asthma (7). Moreover, among asthmatic patients suffering near fatal attacks, both less adaptative personality characteristics (8), along with psychological disturbances, such as denial and anxiety (9, 10), have been described. Finally, asthma mortality appears to be associated with poor control, poor compliance, and an increased incidence of psychosocial morbidity (11).

It is well known that perception of asthma symptoms is subjective and varies widely among individuals: some patients complain of little discomfort with severe bronchoconstriction, while others experience marked discomfort following a small increase in airflow obstruction (12). Importantly, poor perception of asthma severity symptoms may result in undertreatment of the disease (13), and patients that inadequately perceive their symptoms may be at increased risk of experiencing an acute, life-threatening asthma attack (14).

To date, the relationship between personality profiles and behavioral aspects to clinical and functional features of disease has only been examined in patients with extremely severe asthma (7). Additionally, even though psychological and clinical factors could markedly influence how asthmatic patients perceive their symptoms, the literature contains very little data regarding the effects of personality traits of asthmatic patients on their symptoms perception (15). Furthermore, questions still remain as to whether or not any relationship exists between asthma patients' clinical features and breathlessness perception (16, 17).

Our first study aim was to examine whether or not personality profiles and behavioral aspects are related to the clinical and functional features in outpatients with different grading of asthma. We also wished to evaluate whether or not in the same group of patients, breathlessness perception is related to psychological and behavioral factors, as well as to the clinical and functional characteristics of disease.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects

We selected 41 asthmatic outpatients (15 women; age range: 18-52 yr). Patients were consecutively recruited during a 6-mo period and asthma diagnosis was made according to the American Thoracic Society criteria (18). We only included lifetime nonsmoking patients, with no previous history of near fatal asthma attack or hospitalization for asthma. Moreover, subjects did not experience respiratory infections or spontaneous asthmatic relapses during the 4 wk preceding study, and their baseline FEV₁ values had to be greater than 70% of predicted. Two out of the 41 selected outpatients withdrew from the study because they did not satisfactorily complete a symptoms diary card and three out of 41 refused to undergo the psychological evaluation.

In the 36 enrolled patients, treatment at preliminary evaluation included: short-acting ₂-agonists (6), long-acting ₂-agonists (3), oral theophylline (5), antihistamines (2), and a combination of ₂-agonists and low dose inhaled steroids (beclomethasone dipropionate 50 µg per puff) (10). Twenty-six of 36 enrolled patients were receiving antiasthmatic therapy on a regular basis or as needed. However, in all these patients, treatment was inadequate as judged by clinical symptoms and pulmonary function tests. In order to assess asthma severity, we placed participants in a 3-wk run-in period with only ₂-agonists as required. Degree of asthma severity was assessed by a slightly modified version of the asthma severity score proposed by Woolcock and Jenkins (19). Possible scores ranged from 0 to 12. Asthma severity score was based on symptoms, bronchodilator use and daily PEF variability, measured during the three weeks prior to methacholine challenge test day. Briefly, patients' scores were 0 to 4 for symptoms, ranging from no symptoms = 0; symptoms less than once weekly or on exercise = 1; symptoms less than daily or more than once weekly = 2; daily symptoms without nocturnal asthma symptoms = 3; waking at night = 4. Bronchodilator use scores were 0 to 4; ranging from no use = 0; less than once a week = 1; more than daily = 2; 1 to 4 times a day = 3; more than 4 times a day = 4. PEF variability was calculated according to the following formula: highest value-lowest/highest value × 100: scores were 0 to 4, ranging  6% = 0; 6 to 10% = 1; 10 to 15% = 2; 15 to 25% = 3; > 25% = 4. Patients with 0 to 5 scores were classified as having mild disease, 6 to 8 as having moderate disease, and 9 to 12 as having severe disease. For length of asthmatic history, we divided asthmatics in three groups: subjects with newly diagnosed asthma (duration of disease  1 yr), subjects with long asthmatic history and with prolonged history of asthma (duration of disease > 1 yr and  10 yr and > 10 yr, respectively).

Before entering the study, each patient attended a psychological screening interview with a psychologist (B.C.) to rule out any form of present or past mental disorder, according to the Italian version of the Structured Clinical Interview for DSM III-R (SCID III-R) (20) and Structured Clinical Interview for DSM IV Personality Disorders (SIDP IV) (21). No subjects reported histories of cognitive impairment, low instructional level, recent negative life events, and past or present endocrine or metabolic disorder, obesity or recent weight loss, drug or alcohol addiction. Presence of atopy was not a prerequisite for selection. Atopy was assessed by skin prick tests to a standard battery of eight common inhalant allergens. Patients with pollen-related asthma were studied outside pollen exposure. Each patient gave informed and signed consent to participate in the study. Study protocol was approved by the local Ethical Committee.

Methacholine Challenge Test and Breathlessness Perception Study

Methacholine (M) challenge test was performed according to standardized procedure (22). Pulmonary function was measured by a flow-sensing spirometer connected to a computer for data analysis (Vmax 22; Sensor Medics, Yorba Linda, CA). Each subject inhaled doubling increasing concentrations of M (0.03 to 64 mg/ml), nebulized by a dosimeter with an output of 9 ± 0.3 µl/puff (Dosimeter MB3; MEFAR, Brescia, Italy), until FEV₁ was reduced by 20% from post-saline value. Bronchial response to M was expressed as the provocative concentration causing a 20% fall in FEV₁ (PC₂₀ in mg/ml), and was calculated by linear interpolation between the two final points of the log-dose-response curve.

During the methacholine test, intensity of breathlessness was estimated before each FEV₁ measurement with a modified Borg scale labeled from 0 (no symptom) to 10 (maximum bearable). The perception score corresponding to a fall in FEV₁ of 20% (PS₂₀) was calculated by linear interpolation of the last two points on the perception/ fall in the FEV₁ curve of the methacholine challenge test (16). The subjects with a PS₂₀  1 or  5 were respectively defined as hypoperceivers and hyperperceivers, while subjects with a PS₂₀ > 1 and < 5 were defined as normoperceivers (16).

Psychometric Evaluation

Each patient underwent psychometric evaluation with the Italian version of the Minnesota Multiphasic Personality Inventory (MMPI) (23), which consists of 357 statements answered as "true" or "false," as applies to the patient. The scoring results in a standard profile that consists of three "validity scales" and ten "personality scales." The validity scales consist of lie, fake, and defensive responses and validate each profile. Subjects scoring beyond predetermined limits on these scales have answered the test with a bias, invalidating the results of the personality scales. In this study, biased profiles were rejected and not included in the final analysis. The personality scales score characteristics that are based on psychodiagnostic categories. They are not considered to be indicators of psychopathology per se, but personal characteristics somewhat related to the content description of the category. The personality scales consist of hypochondriasis, depression, hysteria, psychopathic deviate, masculinity-femininity, paranoia, psychastenia, schizophrenia, hypomania, and social introversion. Results on the MMPI test are expressed in standardized t scores. Thus, a scale score is considered indicative of psychological dysfunction when t value is < 45 and > 70.

Data Analysis

FEV₁ values were expressed as percent of predicted value. PC₂₀ M values were log-transformed before analysis. Values were presented as mean ± standard deviation (SD) and log-transformed values as geometric mean ± geometric standard error of the mean (GSEM). Differences in numerical data between groups were examined by means of the nonparametric Kruskal-Wallis one way analysis of variance (ANOVA), using the Mann-Whitney U test to assess the significance of differences between pairs of groups where ANOVA showed statistically significant differences. Differences in qualitative data were analyzed by Fisher exact test. Comparisons of proportions were evaluated by means of ² and of ² for trend, when categories of asthma severity or length of history of asthma were taken into account. Relationships were estimated by the Spearman rank correlation coefficient. Multiple regression analysis was performed to assess the contribution of age, sex, presence of atopy, duration of asthma, and asthma severity score to the presence of psychological disturbances and perception of breathlessness. A p value less than 0.05 was considered significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Characteristics of patients who completed the study are shown in Table 1. Baseline FEV₁ values ranged from 70 to 126% and their PEF variability ranged from 2.1 to 29.0%. Moreover, bronchial responsiveness of asthmatics to M, ranged from severe to very mild: PC₂₀ M values ranged from 0.056 to 31.7 mg/ ml. According to the asthma severity score, 12 asthmatics were classified as having mild disease (score range: 2-5), twelve as having moderate disease (score range: 6-8), and twelve as having moderate/severe disease (score range 9-11). When the FEV₁ values of the three asthmatic groups were compared, moderate/severe asthmatics had values significantly lower than mild asthmatics (p < 0.001), but not lower than moderate asthmatics. In the whole asthmatic group, FEV₁ values were negatively correlated to asthma severity score (rs = 0.587; p < 0.001). In addition, moderate/severe asthmatics had PC₂₀ M values significantly lower than mild asthmatics (p < 0.001; Table 1), but not lower than moderate asthmatics. Furthermore, PC₂₀ M values were negatively correlated to asthma severity score (rs = 0.528; p < 0.001). No differences were found between the three asthmatic groups with respect to the duration of disease, presence of atopy, gender, or age.

No specific personality psychological profile could be found in asthmatic patients. In the whole asthmatic group, mean values of MMPI subscale score were within the normal range. When we assessed subscale scores in the three asthmatic groups with different grading of disease, in moderate/severe and moderate asthmatics hypochondriasis subscale scores were at high values of normal range (65.7 ± 12.9 and 64.3 ± 10.8, respectively) and were significantly higher than those of mild asthmatics (54.9 ± 7.4; p < 0.03). Sixteen of 36 asthmatic patients had at least one MMPI subscale score indicative of psychological disturbances (Table 2). When we compared the number of asthmatics with a subscale score indicative of psychological disturbances to that of asthmatics with a normal subscale score, we found a significant trend from mild (2 versus 10) to moderate (6 versus 6) and moderate/severe asthmatics (8 versus 4) (² for trend = 6.075; p < 0.015) (Figure 1). Moreover, when we examined each subscale separately, we found that the asthmatics with a subscale score indicative of hypochondriasis showed a significant trend from mild (0 versus 12) to moderate (3 versus 9) and moderate/severe asthma (5 versus 7) (² for trend = 6.027; p < 0.015) (Figure 2). Furthermore, in all asthmatic patients, hypochondriasis scores were positively correlated to asthma severity score (rs = 0.397; p < 0.02) (Figure 3). Lastly, with respect to the presence of atopy, gender, or age, no difference was found between the asthmatics with at least one subscale indicative of psychological disturbances and those with a normal subscale score. Psychological disturbances were significantly related only to the asthma severity score by multiple regression analysis, namely, the adjusted coefficient of regression was 0.145 (p < 0.02), while the corresponding partial coefficient of regression was 0.25 (p < 0.02).

View larger version (17K): [in this window] [in a new window]   Figure 1.   Comparison between the number of patients who had at least one MMPI subscale score indicative of psychological problems (closed bars) and the number of patients with normal MMPI scale score (open bars) in mild, moderate and moderate/severe asthmatics.

View larger version (18K): [in this window] [in a new window]   Figure 2.   Comparison between the number of patients (closed bars) who had a MMPI subscale score indicative of hypochondriasis score and the number of patients (open bars) with a normal MMPI scale score in mild, moderate and moderate/severe asthmatics.

View larger version (11K): [in this window] [in a new window]   Figure 3.   Correlation between hypochondriasis score and asthma severity score in 36 asthmatic patients. rs = Spearman rank correlation coefficient.

In asthmatic subjects, the PS₂₀ values ranged from 0.1 to 8.1 (mean ± SD: 2.6 ± 2.1). Twelve asthmatics were hypoperceivers and four were hyperperceivers. When we compared the number of hypoperceivers to that of normoperceivers in the three groups of different grading of disease, we found a significant trend from mild (1 versus 9) to moderate (4 versus 6) and moderate/severe asthmatics (7 versus 5) (² for trend = 5.376; p < 0.025) (Figure 4). Two subjects of four hyperperceivers were mild asthmatics and the remaining two were moderate asthmatics. Moreover, when we compared the number of asthmatics with a subscale indicative of psychological disturbances to that of asthmatics with no subscale indicative of psychological disturbances in hypoperceivers (6 versus 6), in normoperceivers (9 versus 11), and in hyperperceivers (1 versus 3), we did not find any difference (² = 0.765; p > 0.05). Lastly, with respect to the presence of atopy, gender, or age, no difference was found between hypoperceivers, normoperceivers, and hyperperceivers. Perception of breathlessness was significantly related only to the asthma severity score by multiple regression analysis, namely, the adjusted coefficient of regression was 0.165 (p < 0.01), while the corresponding partial coefficient of regression was 0.33 (p < 0.01).

View larger version (17K): [in this window] [in a new window]   Figure 4.   Comparison between the number of hypoperceivers (closed bars) and the number of normoperceivers (open bars) in mild, moderate and moderate/severe asthmatics.

In all asthmatics, the duration of disease ranged from 0.5 to 38 yr. Nine subjects were newly diagnosed with asthma, 11 subjects had long asthmatic history and 16 had prolonged history of asthma. When we compared the number of asthmatics with a subscale indicative of psychological disturbances to that of asthmatics with no subscale indicative of psychological disturbances in the three groups with different length of asthmatic history, we did not find any trend from subjects with newly diagnosed asthma (4 versus 5), subjects with long asthmatic history (5 versus 6) and with prolonged history of asthma (6 versus 10) (² for trend = 0.146; p > 0.05). When we compared the number of hypoperceivers to that of normoperceivers in the three groups with different length of asthmatic history, we found a significant trend from subjects with newly diagnosed asthma (5 versus 4) to subjects with long asthmatic history (5 versus 6) and with prolonged history of asthma (2 versus 14) (² for trend = 5.415; p < 0.02). One subject of four hyperperceivers was with newly diagnosed asthma, among the three remaining hyperperceivers two were with long asthmatic history and one subject was with prolonged history of asthma.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

We found that in outpatients with different grading of asthma, the severity of disease is linked to the presence of psychological disturbances and to poor perception of breathlessness, even though we did not observe any specific personality profile for asthmatic patients. Interestingly, among severe asthmatics, we found a significantly higher number of patients with MMPI subscale scores indicative of hypochondriasis when compared to moderate and mild asthmatics. Lastly, we did not find any relationship between personality profiles and breathlessness perception in any patients.

We recruited a group of outpatients affected by asthma with a wide range of baseline airway patency and methacholine bronchial responsiveness, that we classified as mild, moderate, and moderate/severe, according to a score based on symptoms, bronchodilator use and daily PEF variability, over a 3-wk period. We cannot exclude that the degree of asthma severity might be different over a longer period of time. However, we limited the observation period to 3 wk since compliance and accuracy of daily PEF self-assessment for relatively long periods are generally poor (24). To avoid any influence of hospital and intensive care stay on behavior and personality of patients (25), we excluded asthmatic patients with a previous history of hospitalizations for asthma. In our study, psychometric evaluation was obtained by means of MMPI, which is considered to be an "objective" personality assessment because of relatively unambiguous stimuli, which are presented in a question and answer format (26). Our outpatient results showed some similarities with previous studies performed in patients with extremely severe asthma. We confirmed that moderate/severe asthmatic patients have more psychological disturbances than those with mild grading of disease. Two previously conducted studies, which were based on a psychiatric evaluation of patients who had suffered from a near fatal attack of asthma, found a high proportion of asthmatics defined as mentally ill (9, 10). Other reports included asthmatics who experienced near fatal asthma attacks (8), or asthmatics, who despite multiple drug treatment, suffered from persistent unstable asthma (7). In both groups, a higher proportion of mentally ill asthmatics were found when compared with control groups of less severe asthmatic subjects.

In our study, we found that moderate/severe asthmatic patients have more hypochondriasis traits than mild or moderate patients, thus showing the worst coping behavior with the disease. Both agoraphobia and panic disorder were found more common among outpatients with asthma than in the general population (27). Additionally, lifetime history of anxiety disorder was significantly observed more frequently in subjects with brittle asthma than in controls (7). Furthermore, reports regarding patients with a life-threatening attack of asthma showed that subjects can present denial and anxiety (9, 10) as well as poor adaptative personality characteristics (8). Importantly, the style a patient uses to cope with his disease can greatly influence disease developments. In asthmatics, helpless dependency and anxiety or excessive inappropriate independence were related to excessively high hospitalization rates (28). Moreover, in children suffering from asthma, emotional or behavioral deviance was noted to be associated with poor disease control (29). Lastly, denial and consequent noncompliance with treatment or follow-up were considered as contributory etiological factors in fatal or near-fatal asthma (9, 30).

We found that poor perception of breathlessness was associated with severity of asthma, but not to any anthropometric, clinical or functional characteristics of patients. Discordant findings have been previously reported. Symptoms perception differences may derive from different degrees of asthma severity, differences in assessing methods of breathlessness, or cultural differences of the communities studied. In one study, patients with poor or high breathlessness perception were similar for age, sex, and baseline level of airway obstruction or responsiveness (16), whereas in another study, an increase in perception score was related to younger age, more severe airway responsiveness, presence of atopy, and female sex (17). Interestingly, other reports showed that elderly asthmatic patients may be less likely to appreciate the severity of their symptoms (31). Poor perception of acutely induced bronchoconstriction (30) and dyspnea induced by inspiratory resistive loads (32) were found in asthmatics who experienced near fatal asthma. Moreover, a reduced awareness of bronchoconstriction was reported in asthmatic patients who experienced long-standing airflow obstruction (33).

Breathlessness sensation is due to complex and not fully understood mechanisms (34). However, in asthmatic patients, the blunted perception of respiratory symptoms seems to be strictly related to the severity of chronic airway inflammation. Interestingly, in mild to moderate asthmatic patients, more relevant airway inflammatory changes, such as eosinophilic infiltration and epithelial damage, were associated with less breathlessness sensitivity (35). Moreover, the ability to perceive the severity of asthma can be significantly reduced by the duration of its presence. Similarly, in sensory processes, prolonged periods of stimulation result in a consistent reduction in perceived magnitude, which is a process known as temporal adaptation (36).

In conclusion, our study showed that the clinical and functional features of young to middle-aged asthma outpatients with no clinical history of hospitalization are strictly linked to personality profiles and breathlessness perception of patients. Furthermore, among patients with moderate/severe asthma, we found a higher number of patients with psychological disturbances and reduced breathlessness perception than among patients with mild to moderate disease. In addition, the presence of hypochondriasis was related to the severity of the disease in all patients. Our results suggest that the assessment of coping strategies to asthma, along with the measurement of respiratory symptoms perception, can be useful tools for the long-term management of asthmatic patients.