Wheezing in children can have many causes. It is often due to viral infections like RSV bronchiolitis in infants, which causes inflammation and narrowing of the small airways. Asthma is another common cause and presents with recurrent wheezing episodes. Younger children are more prone to wheezing due to their small airway size and lung mechanics. A thorough history, physical exam, and diagnostic testing can help identify the underlying condition causing wheezing to guide treatment.

1. Wheezing in children Dr Divya Nair Department of Pediatrics, Mahavir Hospital & Research Centre, Hyderabad.

2. Introduction Wheeze is a continuous & musical sound that originates from oscillations in narrowed airways Mostly heard in expiration due to critical airway obstruction Sign of lower (intra-thoracic) airway obstruction

3. If there is widespread narrowing of airways leading to various levels of obstruction to airflow (eg. asthma), polyphonic wheeze is heard i.e. sounds of various pitches Monophonic wheeze (single pitch) is produced in larger airways during expiration eg. distal tracheomalacia, bronchomalacia

4. Infants & children are prone to wheeze due to different set of lung mechanics ( as compared to older children & adults) Obstruction to airflow  airway caliber  compliance of lung 1) Resistance = 1/ ( radius of tube)4 In children < 5 years, small caliber peripheral airways can contribute upto 50% of airway resistance Marginal additional narrowing can cause further flow limitation & subsequent wheeze

5. 2) Compliant chest walls, especially in newborns, leads to intra-thoracic airway collapse due to inward pressure produced in expiration 3) Differences in tracheal cartilage composition & airway muscle tone causes further increase in airway compliance

6. All these mechanisms combine to make the Infant more susceptible to airway collapse  Increased resistance  Subsequent wheeze Many of these are outgrown in the 1st year of life itself

7. 4) Immunologic & molecular influences: Infants have increased levels of lymphocytes & neutrophils in BAL fluid Variety of inflammatory mediators have been implicated eg. Histamine, leukotrienes, interleukins, etc Fetal & early post-natal “programming” affects the structure & function of fetal lung by factors including fetal nutrition, fetal & neonatal exposure to maternal smoking

8. DD’s of wheezing: 1) INFECTION: Viral : RSV (Bronchiolitis) Human metapneumovirus Influenza, Parainfluenza Adenovirus Rhinovirus Others: TB Chlamydia trachomatis Histoplasmosis

9. 2) ASTHMA: i) Transient wheezer - risk factor is primarily diminished lung size ii) Persistent wheezers – initial risk factors being passive smoke exposure, maternal asthma history, persistent rhinitis, eczema <1yr age, increased IgE in 1st yr of life At an increased risk of developing clinical asthma iii) Late onset wheezer

10. 3) Anatomic abnormalities: a) Central airway abnormalities: - Malacia of larynx, trachea, bronchi - Tracheoesophageal fistula ( H type) - Laryngeal cleft (leading to aspiration) b) Extrinsic airway anomalies (leading to com- pression): - Vascular ring/ sling - MediastinalLN’pathy (infection/ tumor) - Esophageal foreign body

11. c) Intrinsic airway anomalies: - Airway hemangioma - Cystic adenomatoid malformation - Bronchial/ lung cyst - Congenital lobar emphysema - Aberrant tracheal bronchus - Sequestration - CHD with L R shunt ( pulmonary edema) - Foreign body

12. 4) Immunodeficiency states: - IgA deficiency - B cell defiency - AIDS - Bronchiectasis 5) Mucociliary clearance disorders: - Cystic fibrosis - Primary ciliarydyskinesias - Bronchiectasis

13. 6) BronchopulmonaryDysplasia 7) Aspiration Syndromes - GERD - Pharyngeal/ swallow dysfunction 8) Interstitial lung disease 9) Heart Failure 10) Anaphylaxis 11) Inhalation Injury – Burns 12) WALRTI, Wheeze a/w URTI 13) Drugs: Ibuprofen, Aspirin, Rifampicin, Erythromycin

14. Etiology: I) ACUTE BRONCHIOLITIS: - It is acute inflammation of the airways - predominantly a viral disease - cause: RSV ( > 50%) , parainfluenza, adenovirus, mycoplasma, human metapneumovirus - more common in males, not breast fed, live in crowded conditions - older family members are source of infection - LRTI manifestations are minimal in older patients in whom bronchial edema is better tolerated

15. - RSV infection leads to a complex immune response i) Eosinophilsdegranulate release Eosinophilic Cationic Protein cytotoxic to airway epithelium ii) IgE antibody release may be related to wheezing iii) Other mediators: Chemokines (IL-8, Macrophage Inflammatory Protein); Leukotrienes , IF gamma - Characterized by bronchiolar obstruction with edema, mucus & cellular debris

16. - Resistance in small airway is increased more in exhalation than inspiration  respiratory obstruction  early air trapping & overinflation complete obstruction atelectasis - Hypoxemia occurs early in the course due to VQ mismatch - Hypercapnia develops due to severe obstructive disease and respiratory fatigue

17. II) ALLERGY & ASTHMA: - Important cause of wheezing - Characterized by: airway inflammation, bronchial hyper-reactivity, reversibility of obstruction - 3 identified patterns: a) Transient early wheezer: 20% of population Before the age of 3yrs had wheezing at least once, with LRTI but never wheezed again

18. b) Persistent wheezer: 14% of population Before 3yrs age had wheezing episodes still wheezing at 6yrs age c) Late onset wheezer: 15% of population No wheezing by 3yrs but wheezing by 6yrs - The remaining 50% of children had never wheezed by 6yrs of age

19. III) CHRONIC INFECTIONS: - Should be considered in infants who seem to fall out of range of a normal clinical course - Cystic fibrosis is a common cause - Persistent respiratory symptoms, digital clubbing, malabsorption, FTT, electrolyte abnormalities, resistance to bronchodilator therapy

20. IV) CONGENITAL MALFORMATIONS: - Causes wheezing in early infancy - Findings can be diffuse or focal - Can be from an ext compression/ intrinsic abn - External vascular compression: vascular ring/ sling compressing trachea/ esophagus - CVS causes: massive cardiomegaly, LA enlargement, dilated pulmonary arteries - Pulmonary edema d/t CHF  lymphatic & bronchial vessel engorgement obstruction & edema of bronchioles Wheeze

21. V) FOREIGN BODY ASPIRATION: - Can cause acute/ chronic wheezing - Common between 2mths- 4 yrs of age - Infants may present with atypical histories or misleading radiological/ clinical findings - D/d: asthma, other obstructive disorders - Esophageal FB can transmit pressure to membranous trachea  compromises the airway lumen

22. VI) GASTROESOPHAGEAL REFLUX: - can cause direct aspiration into tracheo- bronchial tree - may trigger a vagal/ neural reflex  increased airway resistance  airway reactivity

23. VII) TRAUMA & TUMORS: - rare causes of wheezing in children - trauma of any type to TB tree (aspiration/ burns/ scalds)  inflammation of the airways  subsequent wheeze - SOL (lung/ extrinsic)  compression  obstruction to airway

24. Clinical Manifestations HISTORY & PHYSICAL EXAMINATION - ODP & associated factors of wheezing: - Birth history: weeks of gestation, NICU admission, h/o intubation/ O2 requirement, maternal complications eg. Infn- HSV, HIV; prenatal smoke exposure - Past medical history: co-morbid conditions eg. syndromes or association

25. - Social history: Environmental history of smokers at home, number of siblings, occupation of inhabitants at home, pets, TB exposure - Family history: of CF, immuno-deficeincy, asthma in 1st degree relatives OR any other recurrent respiratory conditions should be obtained

27. Single parent atopy : 22%Maternal Atopy : 32 %

28. Both parents atopic : 50%(Aberdeen Study 1994)

29. Pertinent medical history in wheezing infant: Did the onset of symptoms begin at birth or thereafter? Is the infant a noisy breather & when is it most prominent? Is there a history of cough apart from wheezing? Was there an earlier LRTI? Have there been any emergency department visits, hospitalizations, or ICU admission for RD? Is there a history of eczema?

30. How is the infant growing & developing? Is there associated failure to thrive? Is there failure to thrive without feeding difficulties? Are there s/o intestinal malabsorption including frequent , greasy, or oily stools? Is there a maternal history of genital HSV infection? What was the gestational age at delivery? Was the patient intubated as neonate? Does the infant bottle feed in the bed or crib, especially in propped position?

31. Are there any feeding difficulties including choking, gagging, arching, or vomiting with feeds? Any new food exposure? Is there a toddler in the home or lapse in supervision in which foreign body aspiration could have happened? Change in caregivers or chance or non accidental trauma?

32. Physical examination: - Vitals especially RR, SPO2 - Growth charts for s/o FTT - Upper airway s/oatopy: boggy turbinates , posterior oropharynxcobblestoning - Evaluate skin for eczema, hemangioma - Midline lesions may be associated with intrathoracic lesions - Clubbing

33. - S/O RD- Tachypnea, nasal flaring, tracheal tugging, SCR/ICR, excessive use of accessory muscles - Prolonged expiratory time, expiratory whistling sounds - Auscultation: aeration to be noted, expiratory wheeze, lack of audible wheeze due to complete airway obstruction - Trial of bronchodilators to evaluate change of wheezing - Stridor +/-.

34. Air Trapping Hyperinflated chest  Barrel shaped  Loss of cardiac dullness  Liver pushed down  Hoover sign Normal diagphragm movement Hyperinflation = diaphragm flattened Diaphragm contraction = paradoxical inward movement of lower interrcostal area during inspiration

35. In Acute Bronchiolitis: - h/o exposure to older contact with URTI  infant 1st develops mild URTI with sneezing & rhinorrhea may be associated with decreased appetite & fever  gradually RD ensues with paroxysmal wheezy cough, dyspnea, irritability

36. - Apnea may be more prominent than wheezing early in the course of disease esp with very young infants ( < 2 mths ) or former premature infants - Degree of tachypnea doesn’t always correlate with degree of hypoxemia/ hypercarbia - Fine crackles/ overt wheezes present - Hyperinflation of lungs palpation of liver & spleen

37. Diagnostic evaluation Initial evaluation depends on likely etiology 1. Chest Xray: hyperinflation, SOL, s/o chronic diseases like bronchiectasis, focal infiltrates 2. Trial of bronchodilators- diagnostic & therapeutic in bronchiolitis & asthma, won’t effect fixed obstruction May worsen wheezing in tracheal/ bronchomalacia 3. Baseline immunity in complicated cases

38. Exclude other conditions 4) Structural problems: bronchoscopy 5) URTD : Polysomnography 6) Esophageal disease: Barium swallow, pH probes, Upper GI scopy 7) Primary ciliarydyskinesia: nasal ciliary motility, Exhaled NO, Electron Microscopy, saccharine test 8) TB: mantoux, induced sputum/ gastric lavage/ BAL = Culture, microscopy & PCR 9) Bronchiectasis: HRCT scan, BAL

39. 10) CF: sweat test, nasal potentials, genotypes 11) Systemic immune deficiency: Ig subtypes, lymphocytes & neutrophil function, HIV 12) Cardiovascular disease: echo, angiography 13) Viral testing (PCR, viral culture) is helpful if diagnosis is uncertain.

40. Treatment 1) Comfort the child – Try to keep your baby calm. Having a cough and a noisy wheeze frightens children and breathing is more difficult when they are upset. 2) Offer frequent liquids – Drinking less but more often may be easier

41. 3) Bronchodilators: - administer inhaled short acting beta-2 agonist (egsalbutamol) & observe the response - Children < 3 yrs: inhaled medications by MDI with mask & spacer, if therapeutic benefit demonstrated - response is unpredictable - Therapy to be continued in all asthma patients with exacerbations with viral illness

42. 4) Ipratropium bromide: - can be used as adjunct therapy - also useful in patients with significant tracheal or bronchomalacia - Anticholinergic agent 5) Oral/ IV steroids: - used for atopic wheezing infants thought to have asthma i.e. refractory to other medications

43. 6) Inhaled steroids: - appropriate for maintenance therapy in known reactive airways but not useful in acute illness - to be used if significant h/oatopy ( food allergy, eczema) present - maintenance treatment with inhaled steroids is recommended for multiple-trigger wheeze.

44. 7) In acute bronchiolitis: - hospitalze - mainstay of treatment is supportive - hypoxemic child: cool humidified oxygen - avoid sedatives - keep head & chest elevated at 30 degree angle - NG tube feeds to avoid aspiration - respdecompensation tracheal intubation - Bronchodilators show modest short term improvement in clinical features - Nebulized epinephrine more effective

45. 8) Montelukast is recommended for the treatment of episodic (viral) wheeze,to be started when symptoms of a viral cold develop 9) Ribavarine: antiviral administered by aerosol - Used for children with CHD/ CLD 10) No role of antibiotics unless secondary bacterial infection

46. Prevention 1) Reduction in severity & incidence of ac. bronchiolitis due to RSV is possible through administration of pooled Hyperimmune RSV Intravenous Immunoglobulin (RSV IVIg, Respigam) and 2) Palivizumab, a monoclonal antibody to the RSV F protein, before & during RSV season It is recommended for children < 2yrs age with chronic lung disease (BPD) or prematurity 3) Inhaled corticosteroids and montelukast may be considered in preschool child with recurrent wheeze.

47. 4) Avoid smoking – Smoking in the home or car increases the risk of respiratory problems in children 5) Educating parents regarding causative factors and treatment is useful. 6) Allergen avoidance may be considered when sensitisation has been established 7) Meticulous handwashing is the best measure to prevent nosocomial infection

48. Prognosis Approx 60% of infants who wheeze, will stop wheezing Ac. Bronchiolitis: highest risk in 1st 2-3 days ; Case Fatality Rate < 1% Death  apnea, severe dehydration, uncompensated resp acidosis Mean duration of symp - 12 days High incidence of wheezing & asthma in children with h/o bronchiolitis CHD/ BPD/ Immuno-deficiency: More severe disease, higher morbidity & mortality

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