1. Asthma Masqueraders: Differential Diagnosis in Children and Teens
Ngoc Ly, MD, MPH
Assistant Professor of Pediatrics
Pediatric Pulmonary Medicine
UCSF Benioff Children’s Hospital

2. Diagnosing Asthma No gold standard for diagnosis Clinical diagnosis
Recurrent respiratory symptoms
Wheeze
Cough
Chest tightness
Breathlessness

5. Symptoms
History
Exam
Spirometric Results
Treatment
Response

6. No Treatment Response Poor compliance or adherence
Severe or difficult asthma
Not asthma

7. Case #1
16 yo girl with 1 year history of recurrent severe dyspnea and wheezing
Multiple ER visits due to severe respiratory distress
Several hospitalizations
Treated with various asthma therapy
No consistent response to therapy

8. Clipping or flattening of the inspiratory loop on spirometry
normal

9. Vocal cord dysfunction (VCD)
Trigger by exercise or emotional stress
Young, female
Dyspnea with exercise
Sensation of tightness in throat rather than chest. Loud wheeze/stridor over larynx rather than chest.
Respiratory distress
Typically no bronchodilator response
Athletes often present with dyspnea during competition but not during their work out.
40% -50% of asthmatic can have VCD
Ref: Ibrahim WH et al, Postgrad Med J 2007

10. Pediatrics 2007;120(4):860

11. Vocal cord dysfunction
Treatment: speech therapy
Ipratropium may block exercise-induced vocal cord dysfunction
Treat underlying conditions, including anxiety, depression, gastroesophageal reflux disease, and rhinosinusitis

12. Exercise-Induced Dyspnea
Outcomes from142 subjects
Median age 14 years (range, 6-21)
Average duration of symptoms of 30.2 months
Male:Female 0.7:1.0
98 patients with prior asthma diagnosis
101 patients were treated including bronchodilators in 96, inhaled corticosteroids in 35, and systemic corticosteroids in 31.
82 had at least 1 urgent medical care visit
Symptoms were reproduced during exercise testing in 117 patients
Mutasim Abu-Hasan et al., ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY 2005

13. Etiology for EID
Symptoms were reproduced during exercise testing in the 117 patients (82% of the 142) who had complete physiologic monitoring and underwent increases in treadmill speed or incline if needed to reproduce symptoms.
Only 11 patients (8%) had evidence of EIA as demonstrated by a significant decrease in FEV1 in association with reproduction of their dyspnea. Eight of those 11 had been previously diagnosed as having asthma.
EID did not occur in 25 patients (18%) who only had 6 minutes of treadmill exercise beyond the warm-up period without further attempts to reproduce their symptoms by further increasing rate and/or incline. None of those 25 patients had exercise-induced bronchospasm despite maintaining a heart rate consistent with 85% of aerobic capacity during the 6 minutes on the treadmill. Since symptoms were not reproduced and physiologic measures other than spirometry were not monitored in these 25 patients, the etiology of their EID was not identified.
74 had normal physiologic limitation: 21 (15%) who met the defined criteria for above normal cardiovascular conditioning, 27 (19%) with cardiovascular conditioning within the defined normal range, and
26 (18%) with poor cardiovascular conditioning.
The well-conditioned group included some highly driven athletes who complain of dyspnea mostly in competitive settings. It appears that their dyspnea was a consequence of their increased ventilatory work due to maximal utilization of their ventilatory capacity with intense exercise. It is also possible that the sensation of dyspnea in these patients was induced or accentuated by anxiety during the competitive athletic activities.
Mutasim Abu-Hasan et al., ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY 2005

14. Exercise Induced Dyspnea
EID not always asthma
Treadmill exercise indicated when
other asthma symptoms not present
Bronchodilator doesn’t prevent EID
Normal baseline lung function
Testing:
Pre- and post-exercise spirometry
Full exercise testing including gas exchange and EKG
Laryngoscopy when indicated

15. Case #2
10 yo girl who developed a cough along with her cousin after they went swimming at a public pool
The following day, she was coughing so much at school that she failed her math test
Kept out of school x2 weeks because the cough was disruptive
Presented to the ED twice
Treated with continuous albuterol, followed by inhaled corticosteroids and allergy medications- no improvement after 4 weeks
Valium, codeine, then antibiotics were prescribed-none were effective
Otherwise healthy, pertussis test negative
Does not cough in her sleep

16. Habit Cough Involuntary, repetitive cough
Loud, dry, “barking” or “honking”
Triggered by infection, irritants, or psychological stressors
Can last for months to years
Disruptive to others-affect school attendance
Cough can be a source of secondary gain but not always
Cough ceases while asleep and usually improves with distraction
Suggestive therapy: the child is asked to hold the cough for 3 seconds initially. After success the amount of time the child is asked to hold his breath is increased to 5 seconds, 10 seconds, etc. up to 60 seconds. When the child gets to 60 seconds usually the desire to cough is gone and the child congratulated on controlling the cough. Can use benadryl,

17. Habit Cough Normal physical exam; normal lung function
Opiods, benzodiazepine, and asthma therapy are ineffective
Treatment: suggestive therapy, self-hypnosis, speech therapy
Suggestive therapy: the child is asked to hold the cough for 3 seconds initially. After success the amount of time the child is asked to hold his breath is increased to 5 seconds, 10 seconds, etc. up to 60 seconds. When the child gets to 60 seconds usually the desire to cough is gone and the child congratulated on controlling the cough. Can use benadryl,

18. Case # 3 9 yo boy present with acute cough 1 week and fever x 2 days
Treated with zithromax and albuterol for audible wheeze
2 weeks later, persistent wheeze, started on oral corticosteroids and inhaled corticosteroids
1 week later no response
CXR taken

19. Foreign Body Aspiration

20. Case # 4
12 yo male
Presenting with 5 days of worsening SOB when lying flat
This progress and was waking him up from sleep
Also wheeze at night
Treated with albuterol and Flovent-no improvement
No SOB during the day, physically active at school
No other complaints
Diagnosed with asthma 2 years prior , using albuterol MDI intermittently
No prior hospitalization

21. Mediastinal Mass
 Mediastinal masses, including tumors, thymic lesions, bronchogenic cysts, angiomatous lesions, and enlarged lymph nodes,

22. Case # 5 7 yo boy with cough x 2 years Harsh, dry, barky cough
Paroxysmal coughing with post-tussive emesis
Awaken from sleep
No response to bronchodilator, corticosteroids, theophylline
Cushingoid from repeated prednisone therapy
Multiple hospitalizations

23. Tracheomalacia Wang CC et al. Ann Thorac Surg. 2010
Pictures taken from: Wang CC, Lu CW, Chen CA, Wu ET, Wu MH, Wang SS, Huang SC. One-stage repair of ventricular septal defect and severe tracheomalacia by
aortopexy and posterior tracheal wall stabilization. Ann Thorac Surg May;89(5):
Wang CC et al. Ann Thorac Surg. 2010

24. Tracheomalacia
Aortopexy-stitching between aorta and sternum to reduce aortal tension on anterior wall of the trachea
Behavioral-successful in mild cases
Albuterol may worsen symptoms due to smooth muscle relaxation
60% of those with TEF have tracheomalacia.

25. Tracheomalacia Most common tracheal defect Expiratory stridor/wheeze
Worse during feeding, crying, or agitation
Improve during sleep
Persistent cough, dyspnea, or tachypnea
Usually resolves by 12 months
R/O vascular compression (ring, sling, anomalous innominate artery)
60% of those with TEF have tracheomalacia.

26. Tracheomalacia

27. Cardiac Wheeze
Cardiac conditions that result in pulmonary artery dilation and/or left atrial enlargement, including large left to right shunts, can compress large airways and cause wheezing.
Left ventricular failure or pulmonary venous outflow obstruction can result in distension of the pulmonary vascular bed, bronchiolar wall edema, increased airway resistance, and wheezing.

28. Cardiac Wheeze Stridor with large airway compression
Wheezing, tachypnea
Recurrent respiratory infections with significant respiratory distress
Apnea
Often tachypnei, May have hypoxemia, Recurrent respiratory tract infections with severe respiratory symptoms.

29. Aspiration Syndromes Chronic cough and wheeze
Swallowing disorders related to neurologic or muscular dysfunction of the pharynx and/or larynx
Chronic microaspiration can cause significant mucosal edema and inflammation
Tracheoesophageal fistula
Swallowing disorders related to neurologic or muscular dysfunction of the pharynx and/or larynx can result in weakness and impaired swallowing, incomplete closure of the glottis, depressed cough reflex, and recurrent episodes of aspiration

30. Case # 7
6 month old boy, term infant, presenting with chronic cough and wheeze only slightly better with asthma medications.
Reflux, gagging and choking with feeds.

31. Posterior laryngeal cleft
Benjamin and Inglis describe type I clefts as a supraglottic, interarytenoid clefts. Type II clefts are a partial cricoid cleft. Type III clefts are a complete cricoid cleft with or without extension into the esophagus and type IV cleft are full laryngotrachealesophageal clefts.
partial
cricoid cleft
complete
cricoid cleft
supraglottic
laryngotracheal-esophageal
clefts

33. Posterior laryngeal cleft
Failure of tracheoesophageal septum development
Chronic cough and wheeze
Respiratory distress with feeds, cyanosis
May present at birth
Aspiration, pneumonia
6% with TEF have PLC
Failure of tracheoesophageal septum development (rostral portion)

34. Posterior laryngeal cleft
GERD must be controlled
Type I clefts can sometimes be managed with speech and feeding therapy aimed towards decreasing aspiration
Endoscopic or open repair
Overall mortality 43%
Type IV clefts: 93% mortality
Endoscopic or open repair when conservative measures fail to prevent aspiration in Type I

35. Other Causes Immune deficiency Cystic fibrosis
Bronchiolitis Obliterans
Interstitial lung diseases

36. Conclusions
Assess
Treat
Reassess if poor response to treatment

37. Go Giants !

38. DIFFERENTIAL DIAGNOSTIC POSSIBILITIES FOR ASTHMA
Upper airway diseases
􀀎 Allergic rhinitis and sinusitis
Obstructions involving large airways
􀀎 Foreign body in trachea or bronchus
􀀎 Vocal cord dysfunction
􀀎 Vascular rings or laryngeal webs
􀀎 Laryngotracheomalacia, tracheal stenosis, or bronchomalacia
􀀎 Enlarged lymph nodes or tumor
Obstructions involving small airways
􀀎 Viral bronchiolitis or bronchiolitis obliterans
􀀎 Cystic fibrosis
􀀎 Bronchopulmonary dysplasia
􀀎 Cardiac disease
Other causes
􀀎 Recurrent cough not due to asthma-habit cough
􀀎 Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux
Need to exclude alternative diagnosis

39. ASTHMA MANAGEMENT Clinical Assessment + - - Pharmacologic Therapy
Comorbid Conditions
Education
ICS
+/-
Other agents
Spirometry
&
Allergy
testing
Triggers
Techniques
Action plan
Response?
Continue Rx
Close F/U
Assess compliance/technique + -
Minimum effective dose
Step-up Therapy
Consider further evaluation
Referral -

40. History Birth history Age of onset Progression Recurrent infections
Relation to sleep
Severe dyspnea, cyanosis, apnea
Eating or feeding difficulties, reflux, FTT
GI symptoms
Cardiac abnormalities

41. Symptoms Cough that goes away with sleep Persistent productive cough
Prominent dizziness, light-headedness, peripheral tingling
Dyspnea with exercise
Persistent tachypnea

42. Exam Normal exam when symptomatic Tachypnea without wheeze
Severe dyspnea without wheeze
Stridor or loud inspiratory wheeze
Spirometry normal or inconsistent with airflow obstruction when symptomatic

43. Case # 5
3 month old girl with noisy breathing, worse when she is agitated or excited, and especially with colds. Normal birth history. Growing and thriving

44. Tracheomalacia Most common tracheal defect Expiratory stridor/wheeze
Worse during feeding, crying, or agitation
Improve during sleep
Persistent cough, dyspnea, or tachypnea
Usually resolves by 12 months
R/O vascular compression (ring, sling, anomalous innominate artery)
60% of those with TEF have tracheomalacia.

45. Double aortic arch
Double aortic arch is most common vascular ring
Caused by persistence of Right and Left IV branchial arches
Rarely associated with Congenital Heart Disease
Symptoms (of tracheal compression or difficulty swallowing) may begin at birth
Right arch is higher, left arch is lower producing reverse S on esophagram in AP
Right arch supplies Right common carotid and Right subclavian arteries
Left arch supplies Left common carotid and Left subclavian arteries
On lateral, arches are posterior to esophagus and anterior to trachea
Arches posterior to esophagus and anterior to trachea

46. Pulmonary Sling
Pulmonary sling occurs because of failure of formation of Left 6th aortic arch so there is absence of Left pulmonary artery
The blood to the Left lung comes from an aberrant Left pulmonary artery which arises from Right pulmonary artery and crosses between esophagus and trachea
Bronchial cyst may produce same finding on esophagus/trachea
Aberrant left pulmonary artery which arises from right pulmonary artery and crosses between esophagus and trachea

47. Bronchomalacia Wheezing can present at birth
More commonly becomes apparent in the first two to three months after birth
The wheezing usually becomes more pronounced with activity or in the setting of upper respiratory tract infections
Albuterol may worsen symptoms due to smooth muscle relaxation
Consider Bronchomalacia in: Premature infant and Patient with poor tone

48. Case # 7
5 month old female infant with Pierre-Robin Sequence, stridor, mild laryngomalacia, FTT, significant reflux
Severe OSA on a sleep study
Chronic cough x 2 months
No gagging or choking with feeds
Bilateral wheeze and crackles on exam