Table 1 Detailed description of collected data and measurements in the DZL All Age Asthma Cohort (ALLIANCE)
Data Collection (Hospital Records, Questionnaires, and Telephone Interviews) | Paediatric Arm | Adult Arm |
Extraction of Routine data | Source: Questionnaires (Baseline and Follow-Up) • study participant: name, gender, city and country of birth, date of birth, birth mode, gestational age, birth weight, birth length, multiple birth, birth order, vaccinations, onset of puberty, physical activity, type of child care, desensitization, measures to reduce allergen exposure, asthma training • demographic and sociodemographic information: mother and father: names, country of birth, contact data (home address, telephone number, email address), country of birth (up to grand-parents), birth year, graduation, professional training, number of children and other persons in same household • feeding (breast-fed, hypoallergenic supplement) • family history (asthma, allergic rhinoconjunctivitis, atopic dermatitis, therapy, comorbidities assessed for parents and grand-parents as well as siblings) • families’ paediatrician name and address as well as of general practitioner | Source: Identification Questionnaire, Screening Questionnaire, Baseline Questionnaire (patient version), Baseline Questionnaire (physician version) • study participant: name, gender, city and country of birth, date of birth, birth mode, multiple birth, desensitization, measures to reduce allergen exposure, asthma training • demographic and sociodemographic information: contact data (home address, telephone number, email address), graduation, professional training, number of persons in same household (current and as child), country of birth of mother and father • feeding (breast-fed) • family history (asthma, assessed for parents and grand-parents as well as siblings) • patient’s pulmonologists name and address • vaccinations • atopy status according to study physician (allergic comorbidities, allergic sensitization without symptoms, no allergies), smoking status (current and former, cumulative pack years), alcohol consumption • comorbidities that might mask severe asthma; cardiovascular and neurologic comorbidities |
Respiratory Symptoms | Source: Questionnaires (Baseline and Follow-Up) • Wheeze and cough ever prior to visit (age of onset, number, duration, severity, triggers, seasonal pattern of symptoms, treatment/medication) • Wheeze and cough during last 12 months prior to visit (number, duration, severity, triggers, seasonal pattern of symptoms, treatment/medication incl. Rout and technique as well as adherence, asthma control, assessed according to GINA [10] guidelines and by ACT [15, 37] • Wheeze and cough in relation to exacerbation (number, duration, severity, triggers of symptoms, treatment/medication) • Asthma Control assessed according to GINA [10], C-ACT, ACT [15, 37] • Allergic and non-allergic comorbidities (allergic rhinitis, atopic dermatitis, food allergy, age of onset, severity, triggers, seasonal pattern of symptoms, treatment/medication) • Medication (ever as well as resolution down to one month during last 12 months prior to routine study visit, resolution down to one day during last 4–5 weeks prior to exacerbation visits) | Source: Baseline and FollowUp Questionnaire (patient version), Baseline and FollowUp Questionnaire (physician version) ACT, ACQ, AQLQ, MFI-20 • first symptoms (age), first diagnosis and disease duration • Asthma Control assessed according to GINA [10], ACT [15], ACQ [16] • Health related quality of life assessed by AQLQ [17] • Fatigue assessed by MFI-20 [18] • Frequency of severe exacerbations, hospital admissions. Mechanical ventilation and asthma-related rehabilitation (ever and previous 12 months) • Allergic and non-allergic comorbidities (allergic rhinitis, atopic dermatitis, food allergy, age of onset, severity, triggers, seasonal pattern of symptoms, treatment/medication) • Current asthma medication (including current dosage of inhaled and oral corticosteroids), important co-medication (ß-blockers, Aspirin), former medication (including immune modulators), desensitization (former or current), work related symptoms |
Environmental Exposures | Source: Questionnaires (Baseline and Follow-Up) • maternal warning signs sub partu (infection, fever, antibiotics or other medication, chorioamnionitis), signs of postpartal infection of child • maternal or paternal smoking during pregnancy and later, further active smoking in household • traffic exposure at home (major street) • mold exposure at home (assessment, refurbishment) • pet exposure at home (type of pet) | Source: Baseline Questionnaire (patient version), Follow-Up Questionnaire (patient version) • maternal or paternal smoking during pregnancy and later, further active smoking in household • mold exposure at home (assessment, refurbishment) • pet exposure in childhood (dogs) |
Objective Measurements | Paediatric Arm | Adult Arm |
Measurements of lung function and inflammation of airways, body composition and physical activity, imaging | 1. Anthropometric data and vital parameters at study date: • Body weight and length, body temperature, heart beats per minute, respiratory rate, oxygen saturation 2. Exhaled breath measurement by electronic nose (e-nose) [21]: • Cyranose 320, Sensigent, Arrow Highway, USA • Main outcome parameters: patterns of volatile organic compounds (VOCs) 3. Exhaled breath measurement by gas chromatography-mass spectrometry (GC-MS) [22]: • Sampling device provided by Fraunhofer ITEM, Hannover • Main outcome parameters: patterns of volatile organic compounds (VOCs) by GC-MS 4. Single- and multiple breath washouts (nitrogen washout with 100% oxygen, O2) [19, 30]: • Ultrasonic flowmeter (EcoMedics AG, Duernten, Switzerland); single- and multiple-breath measurement, mouth-piece, filter, nasal clamp • Main outcome parameters (multiple breath): lung volume (functional residual capacity, FRC), ventilation inhomogeneity (lung clearance index, LCI) • Main outcome parameters (single breath): phase III and IV analysis (SIII/ phase III slope, closing volume) 5. Measurement of exhaled nitric oxide (eNO) [20]: • Rapid-response chemoluminescence analyzer (CLD 88, EcoMedics AG, Duernten, Switzerland); single-breath manoeuvre, filter, no nasal clamp • Main outcome parameter: mean eNO, NO production (eNO x expiratory flow) 6. Spirometry and bodyplethysmography [28, 29]: • Jaeger MasterScreen Body, BD Carefusion, Germany; mouthpiece, filter, nasal clamp • Main outcome parameters: lung volumes (intrathoracic gas volume/functional residual capacity, FRC, total lung capacity, TLC, residual volume, RV), airway resistance, forced expiratory flows and volumes, each before and after bronchodilator 7. Planned: thoracic magnetic resonance imaging (tMRI) | 1. Anthropometric data, vital parameters and body composition at study date: • Body weight and length, waist circumference, body temperature, heart beats per minute, respiratory rate, blood pressure, oxygen saturation, bioimpedance measurement (Nutri Plus, Data-Input GmbH, Darmstadt, Germany) • Main outcome parameters (bioimpedance): Resistance (50 kHz), Reactance (50 kHz), extra cellular mass/ body cell mass index (ECM/BCM Index) 2. Exhaled breath measurement by gas chromatography-mass spectrometry (GC-MS) [22]: • Sampling device provided by Fraunhofer ITEM, Hannover • Main outcome parameters: patterns of volatile organic compounds (VOCs) by gas chromatography-mass spectrometry (GC-MS) 3. Single and multiple breath washouts (nitrogen washout with 100% oxygen, O2) [19, 30]: • VMax ENCORE (Viasys Healthcare), Carefusion Germany; mouthpiece, filter, nasal clamp • Main outcome parameters (multiple breath): lung volume (functional residual capacity, FRC), ventilation inhomogeneity (lung clearance index, LCI) • Main outcome parameters (single breath): phase III and IV analysis (SIII/ phase III slope, closing volume) 4. Measurement of exhaled nitric oxide (eNO) [20]: • Hand-held device (NIOX MINO, Circassia AB, Uppsala, Sweden); single breath manoeuvre, filter, no nasal clamp • Main outcome parameter: mean eNO 5. Bodyplethysmography [33]: • Jaeger MasterScreen Body, BD Carefusion, Germany; mouthpiece, filter, nasal clamp • Main outcome parameters: lung volumes (intrathoracic gas volume/functional residual capacity, FRC, total lung capacity, TLC, residual volume, RV), airway resistance, closing volume, closing capacity 6. Impulse Oscillometry (IOS) [23]: • Masterscreen IOS, BD Carefusion, Germany; mouthpiece, filter, nasal clamp • Main outcome parameters: Resistance (5 Hz, 20 Hz, Frequency dependent resistance FDR), Reactance (5 Hz, AX, Fres) 7. Capnovolumetry [24]: • Masterscreen Capno, Carefusion Germany; mouthpiece, filter, nasal clamp • Main outcome parameters (multiple breath): capnogram phase II and III analysis (Vm2550, SR23), dead space volumes • Main outcome parameters (single breath): capnogram phase II, III and IV analysis (Vm2550, SR23, SIII/ phase III slope, closing volume), dead space volumes 8. Single Breath diffusing capacity (DLCO) [31]: • VMax ENCORE (Viasys Healthcare) and Jaeger MasterScreen Body, BD Carefusion Germany; mouthpiece, filter, nasal clamp • Main outcome parameters: transfer factor of the lung for carbon monoxide (TLCO) and related to alveolar volume (TLCO/VA) 9. Spirometry [29]: • VMax ENCORE (Viasys Healthcare) and Jaeger MasterScreen Body, BD Carefusion Germany; mouthpiece, filter, nasal clamp • Main outcome parameters: forced expiratory flows and volumes, each before and after bronchodilator |
10. Bronchial provocation (Methacholine) [38]: • VMax ENCORE (Viasys Healthcare), Jaeger MasterScreen Body and MasterScreen IOS, BD Carefusion Germany; mouthpiece, filter, nasal clamp • Main outcome parameter: PC20 FEV1, PC40 R5Hz, PC40 FRES 11. Daily Physical Activity (accelerometer based) [25, 26]: • SenseWear Armband, BodyMedia Inc. Pittsburgh (PA), USA • Main outcome parameters: steps per day (SPD) and indicators of daily energy expenditure | ||
Sensitization | Specimen: peripheral blood 1. Measurement of total IgE, eosinophils in white blood cell count 2. Specific IgE (sIgE) measurement by chip technology (Immunocap ISAC 121) [39]: • Immunocap ISAC, Phadia, Uppsala, Sweden • Single components • Main outcome parameter: sensitization pattern to components 3. sIgE measurement by Sandwich-ELISA, Immunocap [40]: • Immunocap, Phadia, Uppsala, Sweden • Allergen extracts • Main outcome parameter: sensitization pattern to extracts 4. sIgE measurement by Immunoblot: • Euroimmun AG, Luebeck Germany • Allergen extracts • Main outcome parameter: sensitization pattern to extracts | Specimen: peripheral blood, skin 1. Measurement of total IgE, eosinophils in white blood cell count 2. Specific IgE (sIgE) measurement by chip technology (Immunocap ISAC 121) [39]: • Immunocap ISAC, Phadia, Uppsala, Sweden • Single components • Main outcome parameter: sensitization pattern to components 3. sIgE measurement by Immunoblot: • Euroimmun AG, Luebeck Germany • Allergen extracts • Main outcome parameter: sensitization pattern to extracts 4. Skin Prick Test • Allergopharma, Hamburg, Germany • Allergen Extracts • Main outcome parameter: sensitization pattern to extracts |
Microbiome | Specimen: skin swabs, nasal swabs, (naso-)pharyngeal swabs, stool samples, induced sputum • Analysis by ultra-high-throughput sequencing • Analysis of microbiota in pharyngeal swab, stool and sputum samples | Specimen: pharyngeal swabs, induced sputum • Analysis by ultra-high-throughput sequencing • Analysis of microbiota in pharyngeal swab and sputum samples |
Viruses, Virome | Specimen: nasopharyngeal swabs • Targeted analysis by virus-specific PCR • Virome by whole-genome sequencing | Specimen: nasopharyngeal swabs • Targeted analysis by virus-specific PCR • Virome by whole-genome sequencing |
Immunology | Specimen: peripheral blood • White blood cell count, high-sensitive CRP, leukocyte subtypes by chip-cytometry [41] • Cytokines, cell-specific (blood cell sub-populations) analyses Specimen: nasal secretions • Cytokines Specimen: induced sputum • Cell subtypes • Cytokines | Specimen: peripheral blood • White blood cell count, high sensitive CRP, leukocyte subtypes by chip-cytometry [41] • Cytokines Specimen: nasal secretions • Cytokines Specimen: induced sputum • Cell subtypes • Cytokines |
Genomics | Specimen: peripheral blood • DNA extraction from whole blood • Analysis of single nucleotide polymorphisms (SNPs) | Specimen: peripheral blood • DNA extraction from whole blood • Analysis of single nucleotide polymorphisms (SNPs) |
Epigenomics | Specimen: peripheral blood (also parents of cases) • DNA extraction from whole blood, cell-specific (blood cell sub-populations) and tissue-specific analyses • Analysis of DNA methylation and histone modification | Specimen: peripheral blood • DNA extraction from whole blood • Analysis of DNA methylation and histone modification |
Transcriptomics | Specimen: peripheral blood, primary nasal epithelial cells • RNA extraction from whole blood or primary cells, cell-specific (blood cell sub-populations) and tissue-specific analyses • Analysis of RNA by array analysis and of candidates by real-time PCR (RT-PCR) | Specimen: peripheral blood, primary nasal epithelial cells • RNA extraction from whole blood or primary cells • Analysis of RNA by array analysis and of candidates by real-time PCR (RT-PCR) |
Metabolomics | Specimen: peripheral blood, urine • Targeted and non-targeted metabolomics from serum and urine samples • Analysis of several hundred human metabolites by HPLC-MS or MS/MS | Specimen: peripheral blood • Targeted and non-targeted metabolomics from serum samples • Analysis of several hundred human metabolites by HPLC-MS or MS/MS |
Lipidomics | Specimen: peripheral blood • Targeted analysis of lipids in peripheral blood • Analysis by LC-MS/MS | Specimen: peripheral blood • Targeted analysis of lipids in peripheral blood • Analysis by LC-MS/MS |
Proteomics | Specimen: peripheral blood • Targeted analysis of proteome in peripheral blood |