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

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

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Symptoms History Exam Spirometric Results Treatment Response

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

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

Clipping or flattening of the inspiratory loop on spirometry normal

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

Pediatrics 2007;120(4):860

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

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

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

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

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

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,

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,

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

Foreign Body Aspiration

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

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

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

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. 2010 May;89(5):1677-8. Wang CC et al. Ann Thorac Surg. 2010

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.

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.

Tracheomalacia

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.

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.

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

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.

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

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)

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

Other Causes Immune deficiency Cystic fibrosis Bronchiolitis Obliterans Interstitial lung diseases

Conclusions Assess Treat Reassess if poor response to treatment

Go Giants !

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

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 -

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

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

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

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

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.

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

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

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

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