- Study protocol
- Open Access
Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project
- Nieves Prior1Email author,
- Eduardo Remor2,
- Carmen Gómez-Traseira1,
- Concepción López-Serrano1,
- Rosario Cabañas1,
- Javier Contreras1,
- Ángel Campos3,
- Victoria Cardona4,
- Stefan Cimbollek5,
- Teresa González-Quevedo5,
- Mar Guilarte4,
- Dolores Hernández Fernández de Rojas3,
- Carmen Marcos6,
- María Rubio7,
- Miguel Ángel Tejedor-Alonso8 and
- Teresa Caballero1, 9
© Prior et al.; licensee BioMed Central Ltd. 2012
- Received: 2 September 2011
- Accepted: 25 June 2012
- Published: 20 July 2012
There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase.
Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains.
To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.
- Hereditary angioedema
- C1 inhibitor deficiency
- Quality of Life
- Qualitative methodology
Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is a genetic disease that reduces the synthesis or function of C1 inhibitor (C1-INH) . Bradykinin acts as the primary mediator . It is considered a rare disease, and in Spain has a minimal prevalence rate of 1.09 cases/100,000 inhabitants . HAE-C1-INH is characterized by recurrent edema attacks affecting different parts of the body (e.g.: face, extremities, gastrointestinal track, upper airway) [1, 4]. The clinical expression is quite variable; patients may be asymptomatic or suffer from life-threatening angioedema episodes with a wide range of disabling symptoms, severe pain or disfigurement. Attacks are unpredictable. Abdominal attacks may mimic acute abdominal emergencies, prompting unnecessary surgery. Mortality is mainly due to upper airway obstruction caused by laryngeal edema and has been reported to be as high as 30-50% in patients with undiagnosed HAE-C1-INH  and 30% in patients diagnosed with HAE-C1-INH whose cases were improperly treated .
Conventional treatment for allergic angioedema with adrenaline, antihistamines and glucocorticoids has not been shown efficacious .
Secondary adverse events and contraindications of treatments in HAE-C1-INH
Secondary Adverse Events
Pregnancy, lactation, childhood, breast cancer, prostate carcinoma, nephrotic syndrome, significant alteration of hepatic function .
Nausea, vomiting, headache, diarrhea, orthostatic regulation disturbances, myositis, muscle necrosis, increase in the risk of thrombosis .
History of thrombosis or thromboembolism .
Fresh frozen plasma
Transmission of infectious diseases, potential aggravation of edema symptoms due to substrate supply that may lead to an increase of bradykinin, alloimmunization, anaphylactic or allergic reactions, excessive intravascular volume with risk of hypervolemia and heart failure .
Potential transmission of infectious and/or pathogenic viruses , infection at injection site and thrombosis associated with indwelling catheters used for the administration of long-term prophylaxis with pdhC1inh concentrate .
Active ischemic heart diseaseIctus in previous 2 weeks .
Anaphylactic and other acute allergic reactions 
Recombinant human C1INH
Allergic reaction .
Rabbit allergy .
The unavailability of some HAE-C1-INH specific therapies, as well as the potential side effects and contraindications of treatments could significantly hinder the management of HAE-C1-INH patients. Moreover, the lack of awareness of HAE-C1-INH among health care professionals may cause patients to fear for their safety and could have a negative effect on health-related Quality of Life (HRQoL).
HRQoL is considered to be a subjective assessment of the impact of disease and treatment across physical, psychological, social and somatic domains of functioning and well-being . Several aspects of HAE-C1-INH (hereditary transmission, improper diagnosis, unpredictability of attacks, disabling symptoms, risk of fatal attacks, unnecessary surgeries, inadequate treatments, frequent need for emergency intervention, lack of information about the disease among health care professionals, adverse effects of treatment or unavailability of specific treatment, etc.) could diminish HRQoL, and the impact of HAE-C1-INH on quality of life should be evaluated. However, there is limited data on this topic in the published literature [24–28]. To the best of our knowledge, a specific instrument for assessing the impact of HAE-C1-INH on HRQoL has not yet been made available.
This HAE-QoL project aims to develop a sound psychometric tool with which to assess HRQoL in HAE-C1-INH. It has been designed with two phases: the first was for developing the draft version of the questionnaire and the remaining phase will be for assessing its psychometric characteristics. Once the instrument has been validated, we will perform a HRQoL study using the final version of the questionnaire.
The results derived from the first phase of the study, in which domains were chosen and items were identified for the first draft of the HAE-QoL questionnaire, are described in this manuscript. We have also included the results of the expert and patient rating phase in which we received feedback for assessing both content and face validity. Lastly, this paper contains the protocol for the future pilot study and psychometric analysis.
Ethical approval was granted by the Research Ethics Committee of Hospital Universitario La Paz (Madrid). HAE-C1-INH patients 18 years or older and HAE-C1-INH experts from different regions of Spain participated in the study. Inclusion criteria for patients, were that they be 18 years old or older and have a confirmed laboratory diagnosis of HAE-C1-INH (type I or II). Exclusion criteria were cognitive disabilities and lack of fluency in Spanish language.
Severity Score (over the last year)
No angioedema episodes and no long term prophylactic treatment.
No life-threatening angioedema episodes, no long term prophylactic treatment and ≤ 6 episodes/year.
No life-threatening angioedema episodes and ≤ 12 episodes/year with long term prophylactic treatment (exclude maintenance treatment with pdhC1INH) or > 6 episodes/year without long term prophylactic treatment.
Life-threatening angioedema episode and/or > 12 episodes/year with long term prophylactic treatment and/or maintenance treatment with pdhC1INH.
The questionnaire was developed according to standard questionnaire development guidelines and methodologies, as well as the protocol for development of a specific HRQoL questionnaire for hemophilia, a disease that has similar characteristics to HAE-C1-INH [29–36]. A patient-centred perspective based on a qualitative methodology was chosen in order to ensure that the content was appropiate and relevant for the target population and did not omit any issues of importance to the HAE-C1-INH patient.
Qualitative interviewing: semi-structured questions answered in interviews with HAE-C1-INH patients and experts
Questions for HAE-C1-INH patients
Without using medical or technical terms, how would you describe your disease?
Name the five aspects of your life that are most important to you.
Of the aspects you have mentioned, which one is the most affected by your disease at this time?
What bothers you most about your disease?
What worries you most about your disease?
What has made you feel upset, pensive or annoyed in relation to your disease?
In what ways does your disease limit you?
Is there anything else that you would like to add about your disease?
Questions for HAE-C1-INH experts:
Without using medical or technical terms, how would you describe HAE-C1-INH?
Name the five aspects of life that in your opinion are the most important for a HAE-C1-INH patient.
Of the aspects you have mentioned, which one is the most affected by HAE-C1-INH?
In your opinion, what aspect of the disease most bothers a HAE-C1-INH patient?
What do you think most worries a HAE-C1-INH patient about his/her disease?
What do you think makes a HAE-C1-INH patient feel upset, pensive or annoyed in relation with his/her disease?
In what ways does the disease limit a HAE-C1-INH patient?
Is there anything else that you would like to add about HAE-C1-INH?
Our HAE-C1-INH patient group (29 females and 16 males) had a mean age of 39 years (18–74 years) and different degrees of HAE-C1-INH severity. These patients and the 8 HAE-C1-INH experts who participated in the study came from 8 regions of Spain (Madrid, Andalusia, Catalonia, Galicia, Asturias, the Valencian Community, Castille and Leon, and the Basque Country).
A content analysis of the interviews identified 240 different responses (verbatims). Subjects referred to relationships with health care professionals, work, studies, family, leisure activities, sport, travel, aesthetics, emotional life, sex life, fear of a fatal episode, death of relatives, and treatment (side effects, availability, and new therapies).
Examples of significant units ( verbatims ) and items
Significant units (Verbatims)
“Few doctors know about my disease”
How often have you felt that health professionals do not know about your disease?
“I am worried about transmitting the disease to my children”
How much do you worry about the transmission of the disease to your children?
“I feel insecure when traveling, due to the unavailability of C1 inhibitor concentrate”
How has your disease limited your traveling?
“The truth is that I am always frightened”
To what extent does your disease make you feel anxious or fearful?
“I am worried about the adverse side effects of medication”
How much are you worried about the adverse side effects of treatment?
“An important aspect that is affected is work. Attacks are more frequent at exam time”
How has your disease affected your work or studies during the last six months?
“Barrier to regulating menstruation”
Have you had problems in receiving adequate treatment for other diseases (drugs for arterial hypertension, oral contraceptives, and other hormonal treatments) due to hereditary angioedema?
“When I have an attack, I cannot walk, wash or groom myself”.
Have your angioedema episodes prevented you from accomplishing basic activities of daily life (washing, eating, walking, etc. ?
“I had to give up medication because of virilization symptoms”
Have you been affected by the possibility of suffering changes in your physical appearance due to the side effects of attenuated androgens?
Category definitions and number of items per category in HAE − QoL questionnaire
N° of items
N° of items
HAE-QOL v 1.0
HAE-QOL v 1.1
To what extent the availability of adequate assistance from health services and the information (related to prevention and treatment) offered by health personnel affects daily life.
To what extent HAE-C1-INH limits physical activities like self-care, grooming, walking, etc.
To what extent HAE-C1-INH interferes with normal social life and leisure activities (including sports, traveling, hobbies).
To what extent HAE-C1-INH affects emotional state/partnership/family.
Objective questions about clinical characteristics of the patient
To what extent HAE-C1-INH interferes with work, studies, or other daily activities, including a worsened performance in these activities, a limitation in the type of activities that can be performed, or difficulties in undertaking of these activities.
To what extent the disease affects physical appearance and aesthetic habits.
To what extent personal health assessment including current health, health perspectives for the future, resistance to disease and the influence of HAE-C1-INH on other aspects of health.
To what extent general mental health, including depression, anxiety, and behavioral and emotional control are affected by HAE-C1-INH.
To what extent HAE-C1-INH treatment affects daily life, regarding disease control, side-effects, availability of treatment.
Characteristics and Severity Score of participating HAE-C1-INH patients (convenience representative sample)
Semi-structured interview phase
Patient rating phase
29 women/16 men
8 women/8 men
18-74 years old (mean age 39)
23-55 years old (mean age 37.4)
Examples of items on HAE-QoL v 1.0 and agreement rates in expert rating phase
How often has the disease prevented you from doing your work or studying properly?
Have you been affected by not knowing how severe an episode of swelling would be?
Modified/Reassigned dimension (to Mental Health)
How often has angioedema impeded your ability to carry out planned activities?
Reassigned dimension to Physical Role
How often have you worried about the possibility that treatment would not be available when you needed it?
To what extent have you felt more at ease after having begun treatment?
Removed (QC, similar to and better wording in item 62)
Examples of items and agreement rates in patient rating phase
To what extent have you been prevented from using other treatments (ACE antihypertensives, oral contraception, …) due to HAE?
Modified (QC also taken into account)
To what extent have you felt at ease after obtaining the HAE diagnosis?
Removed based on QC
How often have you missed work or school/classes because of an angioedema attack?
To what extent have you been affected by the impact of secondary adverse events of attenuated androgens treatment in your physical appearance?
To what extent have you been affected by the need to get to a health care center to receive medication for acute attacks?
Modified based on QC
To what extent has this disease affected you in terms of taking trips or traveling?
In the second phase (working in progress) the preliminary version of the questionnaire presented here will undergo a complete validation process. A psychometric field study will be performed with HAE-QoL v 1.1, SF-36v2 and the specific HAE-C1-INH clinical questionnaire in a sample of HAE-C1-INH patients. Demographic data of the participating patients will also be obtained. Statistical analysis will be performed with the program SPSS/PC Program. Descriptive and psychometric analysis of the questionnaire HAE-QoL will also be performed. The psychometric study will assess data quality (including missing values), scaling assumptions (item variance, item-total correlation, multi-trait/multi-item correlation matrix), reliability (internal consistency and test-retest with calculation of Crombach’s alpha and intraclass correlation index) and evidence for validity. The association between HRQoL as measured by HAE-QoL and different factors that could affect HRQoL will be assessed using Mann–Whitney U test, Krushal-Wallis test or Spearman correlation, as appropriate.
Disease-specific measures to assess HRQoL in HAE-C1-INH patients have not been available until now. This paper describes the initial steps toward developing a disease-specific QoL questionnaire for adults with HAE-C1-INH as part of a national multi-centre research project. Such an instrument can provide a more comprehensive and accurate evaluation of the HRQoL status of HAE-C1-INH patients and insights on how the illness affects their daily life. Moreover, it could be an instrumental tool for building health policies or implementing measures to improve the health and well-being of patients with HAE-C1-INH.
The methodological approach of this study is premised on the idea that a patient´s perception of illness and related impairments is a key issue to consider when assessing HRQoL . Opinions of HAE-C1-INH experts were also used as the basis for item selection. Items were modified or removed based on the responses and feedback provided by patients and experts in order to ensure content validity. Our goal was to create an instrument that patients considered thorough, respondent-friendly and useful for expanding our knowledge of the impact of HAE-C1-INH on HRQoL.
HAE-C1-INH patients and experts were recruited from different regions of Spain in an attempt to gather a variety of perspectives in a country known for its significant geographical and cultural diversity. The questionnaire addressed several dimensions of quality of life on which to base a thorough evaluation. The domain framework is provisional and represents our theoretical model. While the definition or scope of categories (domains) may seem to overlap, future psychometric test results will help us to decide whether to leave the categories as they are or group some of them together under a single broader domain.
Over the last few years, HRQoL has emerged as an important outcome measure of the degree of patient suffering, as well as a tool for comparing the efficacy of different treatments and assessing the results of health policy planning. However, this outcome measure is of little value if the instruments employed lack validity or reliability.
Although generic HRQoL questionnaires are readily available, they often lack the specificity necessary to adequately measure how certain aspects of a disease are related to QoL. In such cases, a disease-specific questionnaire would be preferable.
Data linking HAE-C1-INH to a burden on quality of life has been available for some time , however this is the first time that data has been collected using semi-structured questions. Huang et al.  showed that 46% of HAE-C1-INH patients were dissatisfied with the management of the disease, 85% had a constant fear of airway closure and 65% had a fear of pain. Other studies revealed that disruptive attacks caused patients to miss opportunities for career and personal development and they may have failed to reach their full potential because of high anxiety levels and depression [26–28].
In our study, the issues cited most often by both experts and patients include potentially life-threatening attacks; the adverse side effects of medication (in several cases associated with chronic treatment); the unavailability of acute specific treatment at several health care centres; hereditary transmission; the lack of a known trigger to be avoided in many cases; and the fact that it is a rare disease about which health care professionals know very little. It is especially worth noting that the relevant aspects of HAE-C1-INH were not the same for experts and patients. Aesthetics was an aspect mentioned more often by patients than by experts. On the other hand, experts were more likely to mention the adverse side effects of treatment. This finding supports the general opinion that the clinician´s view of disease severity does not necessarily match with the patient´s perception of disability. Thus, measuring HRQoL impairment could become an important part of HAE-C1-INH management. Moreover, the recent HAE-C1-INH International Working Group consensus has recommended yearly assessments be carried out using a HRQoL questionnaire .
There is limited data available on HRQoL in patients with HAE-C1-INH. Lumry et al.  administered the SF-12 to patients and found that HAE-C1-INH created a considerable humanistic burden across physical and mental health domains. HAE-C1-INH patients also had higher mean scores than population norms in the Hamilton Depression Inventory-Short form (HDI-SF). Over 42% scored >8.5, which is indicative of depressive symptomatology. A determinant factor for depression was the severity of the disease. Patients who were under long term prophylactic treatment with attenuated androgens were shown to report even lower levels of HRQoL when compared with the overall HAE-C1-INH population.
Dermatology Life Quality Index (DLQI), SF-36, and an adaptation of the Pain Disability Index have been used in HAE-C1-INH patients [26, 27], but none of these questionnaires, including the SF-12, have been specifically developed or validated for HAE-C1-INH.
The HAE-QoL questionnaire is a disease-specific HRQoL measure that could be used in future research on clinical and economic matters and the identification of the determinants of HRQoL in HAE-C1-INH. This information could thereby aid health care providers and professionals in their quest to design and implement measures for improving the HRQoL of HAE-C1-INH patients.
The next step in the HAE-QoL project will be to set up a field study using the draft questionnaire (HAE-QoL v. 1.1). We will assess data quality, scaling assumption, reliability and evidences for validity.
Lastly, the final phase of this protocol will be to perform a HRQoL study with the final version of the validated questionnaire. Assessments of HRQoL can be repeated at different times in order to discover how changes in the management of the disease and changes in drug availability influence the HRQoL of HAE-C1-INH patients. We believe this is the first multi-centre research project designed to develop a specific instrument to assess HRQoL in adults with HAE-C1-INH.
NP, TC and ER have made substantial contribution to initial idea and design, acquisition, analysis and interpretation of data, and have been involved in drafting and revising the manuscript. In addition, they have reviewed the manuscript for important intellectual content and have given final approval of the version to be published. CG, CL, RC, JC, AC, VC, SC, TG, MG, DH, CM, MR and MAT have made substantial contributions to the acquisition, interpretation, and analysis of data. They have provided critical reviews of the manuscript and have given final approval of the version to be published. All authors read and approved the final manuscript.
Dr. Nieves Prior, Dr. Carmen Gómez-Traseira1, Dr. Concepción López-Serrano1, Dr. Rosario Cabañas1, Dr. Stefan Cimbollek5, Dr. Teresa González-Quevedo5, Dr. Mar Guilarte4and Dr. Carmen Marcos are members of the Spanish Study Group on Bradykinin-Induced Angioedema (SGBA) (Grupo Español de Estudio del Angioedema mediado por Bradicinina: GEAB).
Dr. Teresa Caballero is an investigator from the IdiPAZ program for promoting research activities (2009), member of the Biomedical Research Network on Rare Diseases U754 (CIBERER) and coordinator of of Spanish Study Group on Bradykinin-Induced Angioedema (SGBA) (Grupo Español de Estudio del Angioedema mediado por Bradicinina: GEAB).
This work has been partially supported by a grant from SEAIC (Spanish Society of Allergy and Clinical Immunology, Type B Grant, 2003) and FIS (Fondo de Investigaciones Sanitarias, Grant n° 060843). Dr. Teresa Caballero is an investigator from the IdiPAZ program for promoting research activities (2009).
We would like to express our appreciation for the help with data collection provided by the AEDAF (Asociación Española de Pacientes con Angioedema Familiar).
- Agostoni A, Aygören-Pürsün E, Binkley K, Blanch A, Bork K, Bouillet L, Bucher C, Castaldo AJ, Cicardi M, Davis AE, De Carolis C, Drouet C, Duponchel C, Farkas H, Fáy K, Fekete B, Fischer B, Fontana L, Füst G, Giacomelli R, Gröner A, Hack CE, Harmat G, Jakenfelds J, Juers M, Kalmár L, Kaposi PN, Karádi I, Kitzinger A, Kollár T, et al.: Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 2004, 114: S51-S131. 10.1016/j.jaci.2004.06.047View ArticlePubMedGoogle Scholar
- Cugno M, Nussberger J, Cicardi M, Agostoni A: Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 2003, 3: 311–317. 10.1016/S1567-5769(02)00162-5View ArticlePubMedGoogle Scholar
- Roche O, Blanch A, Caballero T, Sastre N, Callejo D, López-Trascasa M: Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain. Ann Allergy Asthma Immunol 2005, 94: 498–503. 10.1016/S1081-1206(10)61121-0View ArticlePubMedGoogle Scholar
- Cicardi M, Bergamaschini L, Marasini B, Bocassini G, Tucci A, Agostoni A: Hereditary angioedema: an appraisal of 104 cases. Am J Med Sci 1982, 284: 2–9.View ArticlePubMedGoogle Scholar
- Bork K, Siedlcki K, Bosch S, Schopf RE, Kreuz W: Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc 2000, 75: 349–354. 10.4065/75.4.349View ArticlePubMedGoogle Scholar
- Zuraw BL: Diagnosis and management of hereditary angioedema: an American approach. Transf Apher Sc 2003, 29: 239–245. 10.1016/j.transci.2003.08.008View ArticleGoogle Scholar
- Caballero T, Baeza ML, Cabañas R, Campos A, Cimbollek S, Gómez-Traseira C, González-Quevedo T, Guilarte M, Jurado-Palomo J, Larco JI, López-Serrano MC, López-Trascasa M, Marcos C, Muñoz-Caro JM, Pedrosa M, Prior N, Rubio M, Sala-Cunill A: Spanish Consensus on the Diagnosis, Management And Treatment of Angio-Oedema Mediated by Bradykinin. Part II. Treatment, Follow-Up and Special Situations. J Investig Allergol Clin Immunol 2011, 21(6):422–441.PubMedGoogle Scholar
- Bowen T, Cicardi M, Farkas H, Bork K, Kreuz W, Zingale L, Varga L, Martinez-Saguer I, Aygoren-Pursun E, Binkley K, Zuraw B, Davis HAJ, Ritchie B, Burnham J, Castaldo A, Menendez A, Nagy I, Harmat G, Bucher C, Lacuesta G, Issekutz A, Warrington R, Yang W, Dean J, Kanani A, Stark D, McCusker C, Wagner E, Rivard GE, Leith E, et al.: Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema. J Allergy Clin Immunol 2004, 114: 629–637. Cicardi M (on behalf of PREHAEAT) 10.1016/j.jaci.2004.06.043View ArticlePubMedGoogle Scholar
- Gompels MM, Lock RJ, Abinun CA, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D: C1 inhibitor deficiency: consensus document. Clin Exp Immunol 2005, 139: 379–394. 10.1111/j.1365-2249.2005.02726.xPubMed CentralView ArticlePubMedGoogle Scholar
- Bowen T, Cicardi M, Farkas H, Bork K, Longhurst H, Zuraw B, Aygören-Pürsün E, Craig T, Binkley K, Hebert J, Ritchie B, Bouillet L, Betschel S, Cogar D, Dean J, Devaraj R, Hamed A, Kamra P, Keith PK, Lacuesta G, Leith E, Lyons H, Mace S, Mako B, Neurath D, Poon M, Rivard G, Schellenberg R, Rowan D, Rowe A, et al.: 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary Angioedema. Allergy Asthma Clin Immunol 2010, 6: 24. 10.1186/1710-1492-6-24PubMed CentralView ArticlePubMedGoogle Scholar
- Caballero T, Baeza ML, Cabañas R, Campos A, Cimbollek S, Gómez-Traseira C, González-Quevedo T, Guilarte M, Jurado-Palomo J, Larco JI, López-Serrano MC, López-Trascasa M, Marcos C, Muñoz-Caro JM, Pedrosa M, Prior N, Rubio M, Sala-Cunill A: Spanish Consensus on the Diagnosis, Management And Treatment of Angio-Oedema Mediated by Bradykinin. Part I. Classification, Epidemiology, Pathophysiology, Genetics, Clinical Symptoms and Diagnosis. J Investig Allergol Clin Immunol 2011, 21(5):333–347.PubMedGoogle Scholar
- Cicardi M, Bork K, Caballero T, Craig T, Li H, Longhurst H, Reshef A, Zuraw B: Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy 2012, 67: 147–157. HAWK (Hereditary Angioedema International Working Group): 10.1111/j.1398-9995.2011.02751.xView ArticlePubMedGoogle Scholar
- Caballero T, Farkas H, Bouillet L, Bowen T, Gompel A, Fagerberg C, Bjökander J, Bork K, Bygum A, Cicardi M, de Carolis C, Frank M, Gooi JH, Longhurst H, Martínez-Saguer I, Nielsen E, Obtulowitz C, Perricone R, Prior N: International consensus and practical guidelines on the gynaecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol 2012, 129: 308–320. 10.1016/j.jaci.2011.11.025View ArticlePubMedGoogle Scholar
- Cicardi M, Castelli R, Zingale L, Agostoni A: Side effects of long-term prophylaxis with attenuated androgens in hereditary angioedema: comparison of treated and untreated patients. J Allergy Clin Immunol 1997, 99: 194–196. 10.1016/S0091-6749(97)70095-2View ArticlePubMedGoogle Scholar
- Birjmohun RS, Kees Hovingh G, Stroes ES, Hofstra JJ, Dallinga-Thie GM, Meijers JC, Kastelein JJ, Levi M: Effects of short-term and long-term danazol treatment on lipoproteins, coagulation and progression of atherosclerosis: two clinical trials in healthy volunteers and patients with hereditary angioedema. Clin Ther 2008, 30: 2314–2323. 10.1016/j.clinthera.2008.12.021View ArticlePubMedGoogle Scholar
- Bork K, Pitton M, Harten P, Koch P: Hepatocellular adenomas in patients taking danazol for hereditary angioedema. Lancet 1999, 353: 1066–1067. 10.1016/S0140-6736(99)00110-5View ArticlePubMedGoogle Scholar
- Crampon D, Barnoud R, Durand M, Ponard D, Jacquot C, Sotto JJ: Danazol terapia: an unusal aetiology of hepatocelular carcinoma (letter). J Hepatol 1998, 29: 1035–1036. 10.1016/S0168-8278(98)80140-2View ArticlePubMedGoogle Scholar
- De Serres J, Gröner A, Lindner J: Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert ® P) in hereditary angioedema: a review. Transf Apher Sci 2003, 29: 247–254. 10.1016/j.transci.2003.08.006View ArticleGoogle Scholar
- Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W: Treatment of acute edema attacks in hereditary Angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol 2007, 119: 1497–1503. 10.1016/j.jaci.2007.02.012View ArticlePubMedGoogle Scholar
- Firazyr®: (icatibant acetate) [package insert]. Jerini AG, Berlin, Germany; 2009.Google Scholar
- Caballero T, López-Serrano C: Anaphylactic reaction and antibodies to DX-88 (kallikrein inhibitor) in a patient with hereditary angioedema. J Allergy Clin Immunol 2006, 17: 476–477.View ArticleGoogle Scholar
- Zuraw BL: Novel therapies for hereditary angioedema. Immunol Allergy Clin North Am 2006, 26: 691–708. 10.1016/j.iac.2006.09.007View ArticlePubMedGoogle Scholar
- Revicki DA, Osoba D, Faiclough D, Barofsky I, Berzon R, Leidy NK, Rothman M: Recommendations on health-related quality of life research to support labelling and promotional claims in United States. Qual Life Res 2000, 9: 887–900. 10.1023/A:1008996223999View ArticlePubMedGoogle Scholar
- Poon E, Seed PT, Greaves MW, Kobza-Black A: The extent and nature of disability in different urticarial conditions. Br J Dermatol 1999, 140: 667–671. 10.1046/j.1365-2133.1999.02767.xView ArticlePubMedGoogle Scholar
- Huang SW: Results of an on-line survey of patients with hereditary angioedema. Allergy Asthma Proc 2004, 25: 127–131.PubMedGoogle Scholar
- Bygum A, Andersen KE, Mikkelsen CS: Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol 2009, 19(2):147–151.PubMedGoogle Scholar
- Kreuz W, Martinez-Saguer I, Aygören-Pürsün E, Rusicke E, Heller C, Klingebiel T: C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis. Transfusion 2009, 49: 1987–1995. 10.1111/j.1537-2995.2009.02230.xView ArticlePubMedGoogle Scholar
- Lumry W, Castaldo AJ, Vernon M, Blaustein MB, Wilson DA, Horn PT: The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity and depression. Allergy Asthma Proc 2010, 31: 407–414. 10.2500/aap.2010.31.3394View ArticlePubMedGoogle Scholar
- Eignor DR: Standards for the development and use of tests: the standards for educational and psychological testing. Eur J Psycho Assess 2001, 17: 157–163. 10.1027//1015-5718.104.22.168View ArticleGoogle Scholar
- Remor E: Development of a disease-specific measure to the assessment of quality of life in adult patients living with hemophilia in Latin America: the HemoLatin-QoL. Interam J Psychol 2005, 39: 211–220.Google Scholar
- Arranz P, Remor E, Quintana M, Villar A, Díaz JL, Moreno M, Monteagudo J, Ugarriza A, Soto I, Pérez R, Chacón J, García-Luaces M, Cid A, Balda I, López MF, Gutiérrez MJ, Martínez E, Marrero C, Prieto M, Sedano C, Vaca R, Altisent C, Hernández-Navarro F, The Hemofilia-QoL Group: Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia. Haemophilia 2004, 10: 376–382. 10.1111/j.1365-2516.2004.00918.xView ArticlePubMedGoogle Scholar
- Remor E, Baldellou A, Dalmau J, Feitos-Caldas C, Fernándes-Epifanio J, Fornell J, Grascia M, Sanjurjo P, Garcia H: Quality of life and adolescents with Gaucher disease. Proposing a new measure: Gaucher-QoL questionnaire. Psychol Health 2005, 20: 224.Google Scholar
- Krippendorf KL: Content analysis: an introduction to its methodology. Sage, Beverly Hills, CA; 1980.Google Scholar
- Boyatzis RE: Transforming Qualitative Information. Sage Publications, Thousand Oaks, CA; 1998.Google Scholar
- Gill TM, Feinstein AR: A critical appraisal of the quality of quality-of-life measurements. JAMA 1994, 272: 619–626. 10.1001/jama.1994.03520080061045View ArticlePubMedGoogle Scholar
- Scientific Advisory Committee of the Medical Outcomes Trust: Assessing health status and quality-of-life instruments: Attributes and review criteria. Qual Life Res 2002, 11: 193–205. 10.1023/A:1015291021312View ArticleGoogle Scholar
- Schipper H, Clinch J, Powel V: Definitions and conceptual issues. In Quality of life assessment in clinical trials. Edited by: Spilker B. Raven Press, New York; 1990:11–24.Google Scholar
- Greaves MW: Skin diseases with high public health impact. Urticaria and angioedema. Eur J Dermatol 2008, 18: 105–106.PubMedGoogle Scholar
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