Respiratory comorbidities in severe asthma: focus on the pediatric age

Figures & data

Table 1. Main respiratory comorbidities of asthma, including clinical symptoms, pathogenetic mechanisms, screening tools and current/promising therapies.

DISEASE	SYMPTOMS AND SIGNS		PATHOGENESIS	SCREENING TOOLS	CURRENT / FUTURE THERAPIES
UPPER AIRWAYS
AR	Nasal itch and congestion Sneezing Rhinorrhea Post-nasal drip		IgE-mediated type 2 inflammation	SNQ CARAT CARATkids	Trigger avoidance nasal rinses topic or systemic H1-antihistamines INCS
NAR Infectious Non infectious			Eosinophilic, neutrophilic and/or mast-cell nasal infiltrates		AIT Anti-IgE Anti-IL4 and IL-13 Anti-TSLP, anti-IL25 and anti-IL33
CRS CRSwNP CRSsNP	Nasal obstruction Nasal discharge Facial pain Facial pressure Smell loss Cough		Eosinophils, ILC2, TH2, mast-cells, basophils Neutrophils, IL6, IL8, IL17, TNFα	SNOT-22 SNQ EP30S	NSAIDs Endoscopic sinus surgery Anti-IgE Anti-IL5/IL-5Rα Anti-IL4 and IL-13 Anti-ILC2 and anti-TSLP
OSA	Attention deficit Behavioral alterations Daily sleepiness Gasping Nighttime sweating Enuresis Snoring Nocturnal dyspnea		Vagal hypertone T-cell infiltration IL-6 TFNα CRP	PSQ Berlin Questionnaire STOP-Bang questionnaire	cPAP Weight loss Positional therapy Maxillofacial expanders ICS Anti-leukotrienes
ILO	Stridor Syncope Throat tightness Dry cough Glottic wheeze		Abnormal glottic abduction or supraglottic narrowing in response to harmless stimuli Abnormal glottic abduction during exercise	VCDQ PVCDI PVFMD-SQ	Breathing exercises CPAP Intubation Heliox Speech therapy
EILO	Dyspnea during exercise				Botulin injections Psychotherapy Supraglottoplasty Inhaled anticholinergics
MIDDLE-TO-LOWER AIRWAYS
BREATHING PATTERN DISORDERS	Disproportioned dyspnea at rest Breathlessness Frequent yawning Frequent sighing Chest tightness Short expiratory breath-holding times	Stress-induced vagal hypertone Hypocapnia Increased individual sensitivity to airway caliber changes		Nijmegen Questionnaire BPAT Structured light plethysmography	Patient reassurance Breathing techniques Lotorp method Cognitive behavioral therapy Mindfulness techniques
FUNGALDISEASES AFRS SAFS CFB CFB/SAFS ABPM ABPA	Recurrent wheezing Productive cough Hemoptysis Low-grade fever Weight loss Malaise Black mucus plugs	Fungal hypersensitivity Airways colonization Epithelial damage Type-2 inflammation Oxidative stress		None	Long-term OCS Anti-fungal (controversial) Macrolides Anti-IgE Anti-IL33 ST2-antagonists Anti-endothelin-1R anti-IL17Rα
BE	Productive cough Mucopurulent sputum RLRI Dyspnea Wheezing	Chronic neutrophilic and/or eosinophilic inflammation Impaired mucociliary clearance Increased mucus production Airways remodeling		Bronchiectasis severity index Longitudinal HRCT	Inhaled hyperosmolar agents Airway clearance techniques Pulmonary rehabilitation Long-term macrolides

ABPA: allergic bronchopulmonary aspergillosis; ABPM: allergic bronchopulmonary mycosis; AFRS: allergic fungal rhinosinusitis; Anti-endothelin-1R: anti-endothelin-1-receptor; AIT: allergic immunotherapy; AR: allergic rhinitis; BE: bronchiectasis; BPAT: Breathing Pattern Assessment Tool; CARAT: Control Allergic Rhinitis and Asthma Test; CARATkids: Control Allergic Rhinitis and Asthma Test in children; CFB: chronic fungal bronchitis; cPAP: Continuous Positive Airway Pressure; CRP: C-reactive protein; CRS: chronic rhinosinusitis; CRSsNP: chronic rhinosinusitis without nasal polyposis; CRSwNP: chronic rhinosinusitis with nasal polyposis; EILO: exercise induced laryngeal obstruction; EP30S: European Position Paper on Rhinitis and Nasal Polyposis Questionnaire; HRCT: high resolution computer tomography; ICS: inhaled corticosteroids; IgE: immunoglobulin E; IL: interleukin; anti-IL17Rα: interleukin-17 receptor alpha; ILO: inducible laryngeal obstruction; INCS: intranasal corticosteroids; NAR: nonallergic rhinitis; NSAIDs: non-steroidal anti-inflammatory drugs; OCS: oral corticosteroids; OSA: obstructive sleep apnea; PSQ: Pediatric Sleep Questionnaire; PVCDI: Pittsburgh Vocal Cord Disfunction Index; PVFMD-SQ: Paradoxical Vocal Fold Movement Disorder Screening Questionnaire; RLRI: recurrent lower respiratory infections; SAFS: severe asthma with fungal sensitization; SNQ: sinonasal questionnaire; SNOT-22: sinonasal outcome-test-22; STOP-Bang: snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender; TH2: T helper 2 cells; TNFα: tumor necrosis factor alpha; TSLP: thymic stromal lymphopoietin; VCDQ: vocal cord dysfunction questionnaire