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The self-assessment of perceived immune status is important, as this subjective observation leads individuals to decide whether or not to seek medical help or adapt their lifestyle. In addition, it can be used in clinical settings and research. The aim of this series of studies was to develop and validate a short questionnaire to assess perceived immune functioning. Five surveys were conducted among Dutch and International young healthy adults (18–30 years old), and two others among older age groups with various health complaints. For the first study, an existing immune functioning scale was modified and elaborated resulting in 23 immune-health-related items, of which the occurrence was rated on a 5-point Likert scale. A student sample was surveyed, and the results were used to shorten the 23-item listing into a 7-item scale with a predictive validity of 85%. Items include “sudden high fever”, “diarrhea”, “headache”, “skin problems (e.g., acne and eczema)”, “muscle and joint pain”, “common cold” and “coughing”. The scale is named Immune Status Questionnaire (ISQ), and it aims to assess perceived immune status over the preceding year. The second study revealed that the ISQ score correlated significantly with a 1-item perceived immune functioning (r = 0.383, p < 0.0001). In the third study, the final Likert scale descriptors were determined (“never”, “sometimes”, “regularly”, “often” and “(almost) always)”. The fourth study showed that the test–retest reliability of the ISQ is acceptable (r = 0.80). The fifth study demonstrated the association of ISQ scores with various neuropsychological and health correlates in an international sample, including perceived health and immune fitness, as well as levels of stress, fatigue, depression and anxiety. Study 6 demonstrated significant associations between ISQ scores and experiencing irritable bowel syndrome (IBS) symptoms in a sample of insomnia patients. Study 7 compared the effect of a dietary intervention in participants reporting “poor health” versus “normal health”. It is shown that ISQ scores can differentiate between those with poor and normal health, and that an effective intervention is associated with a significant improvement in ISQ scores. Data from Study 7 were further used to determine an ISQ cut-off value for reduced immune functioning, and a direct comparison with 1-item perceived immune functioning scores enabled constructing the final scoring format of the ISQ. In conclusion, the ISQ has appropriate face, content, and construct validity and is a reliable, stable and valid method to assess the past 12 month’s perceived immune status.
Keywords: immune functioning, questionnaire, perceived immune status, fitness, ISQAn adequately functioning immune system is essential for the body to recognize and defend itself against exposure to external agents, including bacteria, viruses and substances (e.g., alcohol and drugs). Various environmental factors, lifestyle and behaviors can affect immune functioning, both positively and negatively [1]. Exposure to psychological factors (e.g., stress) can also impact immune functioning. The immune system plays an important role, either positive or negative, in various diseases and disorders and is an important health determinant [2,3,4,5,6,7,8,9,10]. For example, altered immune functioning may have a pronounced effect on normal physiological processes but is also involved in the pathology of various chronic diseases as well as certain psychiatric disorders such as depression and autism [11,12]. A combination of neuroinflammatory, neuroendocrine and metabolic effects can result in reduced immune functioning and subsequently have a negative impact on wellbeing and quality of life [6,8,13]. To identify people at risk for disease [14], assessing how well the immune system functions, i.e., immune fitness, is important to enable early intervention, for example.
There are several ways to evaluate immune functioning. The most frequently used involve objective qualitative and quantitative assessments in blood, e.g., counts of the type and number of immune cells, immune mediators such as cytokines, chemokines and/or antibodies [14,15]. Such measures are relative costly, time-consuming and invasive. Even noninvasive assessments in saliva or urine require specialist resources and can be regarded as an imposition on those being assessed. Additionally, there is usually a time delay before results are available.
Perhaps more important, these objective assessments are often not informative about how participants experience their immune fitness, or how they feel (e.g., mood or quality of life). The latter can only be determined by subjective assessments, i.e., asking the patients how they feel. These experiential factors represent the most important determinants for participants to judge if they feel sick or healthy, and consequently seek medical help or advice [16]. These factors led us to develop a self-assessment instrument of immune fitness. This has ramifications for clinical practice, for example to determine whether further biomarker assessments are warranted.
Such a self-assessment questionnaire has multiple potential applications, since it can be used in clinical practice, for research proposes, as well as by an individual for self-assessment. The outcome of the questionnaire is not only useful to screen for an increased risk of immune-related disease but can also influence one’s decision to seek medical attention or adapt their lifestyle. The development of such a questionnaire is essential, since a growing number of chronic diseases and disorders are linked to alterations in the immune system [17,18].
There are several scales developed to assess immune status, including the 1-item perceived immune functioning rating, which is used as a comparator in the studies reported here. The 1-item perceived immune functioning rating has been used in several studies as a measure of current immune fitness and showed to correlate significantly to various health outcomes, including ratings of sleep disturbance, autism, general health, mental resilience and irritable bowel syndrome (IBS) [16,19,20,21,22]. The 1-item has the advantage of being simple to administer and is currently the quickest method of determining perceived immune functioning. As a momentary assessment, however, it is by definition limited to the current perception of immune fitness. It also does not provide any information about the possible underlying cause(s) related to the outcome.
The Immune Fitness Questionnaire (IFQ) [23] served as the basis for developing the Immune Status Questionnaire (ISQ). The IFQ does provide information about the underlying cause as it includes multiple items. A study introducing the IFQ revealed significant associations of IFQ scores with the number of general physician visits, general health and experiencing problematic internet use [23]. Although it has not been used in clinical practice, our group used the IFQ in two of our studies [19,22]. This led to the identification of certain shortcomings. Specifically, the IFQ does not capture some of the common aspects of a compromised immune function, such as muscle and joint pain or the common cold. On the other hand, it does include some relatively less common items, such as meningitis, slow healing wounds and boils.
The immune system assessment questionnaire (ISAQ) was developed as an alternative scale [24]. The ISAQ is an elaborate questionnaire with high specificity but moderate sensitivity to identify immune dysfunction. Sievers et al. [18] altered the ISAQ to obtain the infectious disease questionnaire (or “ID screen”). The ID screen is used to investigate infectious diseases and their risk factors, rather than overall immune functioning. Although it has been more extensively validated, it is not a suitable alternative for the ISQ, largely because it specifically targets identification of infectious disease rather than overall immune status. Finally, the Sickness questionnaire (SicknessQ) of Andreasson et al. [17] was developed to investigate symptoms of immune activation related to sickness behavior. Andreasson reported significant associations between SicknessQ scores and depression, anxiety, self-rated health and a single item of feeling sick. Despite the development of these questionnaires, a literature search did not identify any studies using the IFQ, ISAQ, the ID screen or the SicknessQ in clinical practice. This may be caused by the fact that the scales were elaborate and focusing on specific aspects of immune symptom functioning (e.g., infectious disease risk) rather than providing a global rating of general immune fitness assessed over a relevant period of time (e.g., the past year). Therefore, the aim of the current series of studies was to develop, validate and implement a short and cost-effective immune status questionnaire, with applicability in multiple settings, including clinical practice, research and self-assessment.
To develop and validate the ISQ, five studies were conducted. The ISQ was implemented in two subsequent studies [25,26]. The seven studies (summarized in Figure 1 ) are detailed in following sections. The studies were conducted by Utrecht University and the Ethics Committee of the Faculty of Social and Behavioral Sciences of Utrecht University granted ethical approval (approval code FETC17-061).