Pediatric Asthma Making the Diagnosis by n3NYd0M


									The Care of Children with Acute and
 Chronic Respiratory Diseases and
  Physical Therapy Interventions

       Jonathan Popler, M.D. FAAP, FCCP
     Georgia Pediatric Pulmonology Associates
      American Physical Therapy Association

• Discuss the presentation and underlying
  pathophysiology of pediatric respiratory
  diseases in both the acute and chronic care
  At the end of the presentation, participants should
  be able to:
• Identify typical pediatric pulmonary diseases
  found in acute and chronic care settings
• Understand the underlying pathophysiology of
  common pediatric pulmonary diseases
• Identify pediatric patients with pulmonary disease
  in whom physical therapy intervention and
  rehabilitation services would be successful
      What are Typical Pediatric
       Pulmonary Diseases?
• Asthma
• Cystic Fibrosis
• Respiratory complications from Sickle Cell
• Respiratory Complications from
  neuromuscular Disease
Kids can be unpredictable!

          Asthma Capital
          of the United States!!!
                  What is Asthma?
“Asthma is a chronic inflammatory disorder of the airways in which many
  cells and cellular elements play a role: in particular, mast cells,
  eosiniphils, T lymphocytes, macrophages, neutrophils, and epithelial
  cells. In susceptible individuals, this inflammation causes recurrent
  episodes of wheezing, breathlessness, chest tightness, and coughing,
  particularly at night or in the early morning. These episodes are
  associated with widespread but variable airflow obstruction that is
  often reversible either spontaneously or with treatment. The
  inflammation also causes an associated increase in the existing
  bronchial hyperresponsiveness to a variety of stimuli. Reversibility of
  airflow limitation may be incomplete in some patients with asthma.”
  (EPR 1191; EPR-2 1997)
           What is Asthma?
Asthma is a chronic inflammatory disorder of
 the airways which causes recurrent episodes
 of wheezing, breathlessness, chest tightness,
 and coughing, particularly at night or in the
 early morning. These episodes are often
 reversible either spontaneously or with
Asthma is the Most Common Chronic Illness
of Childhood
•Highest-ranking chronic condition resulting in hospitalization
•31% of ER visits for asthma in 1998 were children under 14
•An estimated 6 million children have asthma
•In Georgia, 75,000 children missed 470,000 days of school
•Asthma deaths in children between the ages of 5-14 doubled
between 1980 and 1993
in Childhood

  6 – 7 million children with asthma
Estimated costs of asthma in 2007

      Hospital care: $4.7 billion
    Physician Services: $3.8 billion
    Prescription drugs: $6.2 billion
Asthma is Underdiagnosed and therefore
Undertreated in Infants and Children
•Children with asthma are often mislabeled as having recurrent
bronchitis, bronchiolitis or pneumonia.
•The diagnosis of asthma is not needed to consider and begin
to treat wheezing in children.
•Upper respiratory viral infections are the most common
precipitant of wheezing and cough in this age group, and do
not preclude the diagnosis of asthma.
                Risk Factors
       MAJOR                    MINOR

• Atopic dermatitis     • Allergic Rhinitis

                        • Eosinophilia
• Maternal history of
  asthma                • Wheezing without
Racial Differences in Physiologic Parameters
of Asthma

Middle-class African American Children with Asthma
•Decreased FVC and FEV1
•Increased Airway Responsiveness
•Increased total serum IgE levels
(In comparison with a matched cohort of European-
American Children with Asthma)
                              Joseph et al, CHEST, 2000
                                     Age Adjusted Death Rates
                                                            5 to 34 yo


Death Rate per

                 8                  Total

                 6                  Whites













                            Source:CDC Mortality Statistics 1992; 1998
      2007 NHLBI ASTHMA
• New categories created for children ages
  birth to 4 yrs, 5 – 11 yrs, and 11 –18 yrs

• Emphasis placed on assessing risk and
  impairment, not just “severity”
Treat the symptoms….or should we?
        Why treat young children…..?

Young children are at high risk for severe

Childhood asthma has
the potential to persist
and/or relapse

Chronic changes of
asthma can develop in
the preschool years
            IgE Sensitization
• Allergic reactions       • Immediate reaction
  require EXPOSURE           induces typical allergy
  and SENSITIZATION          symptoms
• Must be exposed for a
  period of time
• Indoor allergens :       • Late phase reaction
  younger than age 2 yrs     induces “priming” of
• Outdoor allergens : 3-     the nasal mucosa
  5 yrs                      becomes
         Cough and Asthma
• Nocturnal Cough

• Cough first thing in the morning

• Cough during or after exercise

• Exercise Coughing : Uncontrolled
   asthma or Exercise Induced Asthma
      Inhaled Corticosteroids
• Nebulized
  – Budesonide
• Metered Dose Inhalers
  – Fluticasone, Beclomethasone, Ciclesonide,
    Combination therapies
• Dry Powder Inhalers
  – Fluticasone, Mometasone, Budesonide,
    Combination therapies
         Stepping UP Therapy
Follow up is essential
   2 – 6 weeks after starting therapy
   Every 1 - 6 months once control established

Reassess Severity

Before making changes :
  Assess compliance
  Assess technique
  Assess knowledge
        Stepping UP Therapy
• Addition of other drugs versus increasing

• In young children, preferred to first increase

• Addition of montelukast versus LABA

• Assess co-morbities (particularly rhinitis)
           Other Considerations

• Allergy Testing
   – Trigger Avoidance
   – Omalizumab (Xolair)
   – Immunotherapy

• Other diagnoses
   –   Cystic Fibrosis
   –   Sinusitis
   –   GER
   –   Vocal Cord Dysfunction
   –   Laryngomalacia
    Massage Therapy in Asthma
• Sixty (60) children with asthma were divided randomly
  into two equal groups: massage therapy group and control
• Subjects in the massage therapy group received a 20-
  minute massage therapy before bedtime every night for 5
• Spirometry was performed for all children on the first and
  last days of the study
• At the end of the study, mean FEV1 of the
  massage therapy group was significantly higher than
  controls (2.3-0.8 L versus 1.9-0.9 L, p=0.04).

                                      Fattah MA J Altern Complement Med. 2011
       Physical Activity in Pediatric
• Comparison of baseline and post-intervention activity levels among 59
  children aged 10-16 with well-controlled asthma and 59 healthy
  matched controls, Participants completed
  spirometry, physical examination, anthropometric measurement, and
  psychosocial questionnaires.
• Participants wore blinded calibrated pedometers for a baseline typical
  activity week
• Similar rates of objectively measured physical activity among youth
  with well-controlled asthma and controls
• The intervention was successful even among typically sedentary
  groups, and represents an effective, safe, and inexpensive walking
  program, even for asthmatic children.

                                             Walders-Abramson N, Wamboldt FS, Curran-
                                             Everett D, Zhang L. Pediatr Pulmonol. 2009
Moderate and vigorous exercise
programs in children with asthma
• Children with asthma (7-14 years old) were randomized to
  a 9-week swimming or golf program.
• Combined group analysis revealed that only six symptom
• Post-exercise decreases were observed in asthma symptom
  severity scores (9.3-7.3, P < 0.001), improved parental
  QOL (4.9-5.4, P < 0.001), and reduced urgent physician
  visits for asthma (1.3-0.2 visits per person, P = 0.04).
• Vigorous and moderate-intensity physical activity
  programs are well-tolerated, safe. Participants and parents
  reported reduced childhood asthma symptoms and
  physician office visits and improved parental QOL.
• These findings suggest a potentially beneficial role for
  moderate to vigorous physical activity in childhood
                                   Weisgerber M, et al. Pediatr Pulmonol. 2008.
    Cystic Fibrosis in the Pediatric
• Chronic sinus and pulmonary infections and
  malabsorptive symptoms
• Median predicted survival to the mid 30s
• CF gene encodes for the cystic fibrosis
  transmembrane conductance regulator
  (CFTR) protein, which functions as an ion
  channel and controls the movement of salt
  and water into and out of cells
            Genetics of CF
• Autosomal recessive inheritance
• Gene on chromosome 7
  – Over 1,000 mutations have been identified
  – F508 is the most common mutation
         How is the diagnosis of CF
• Should be suspected in any patient with chronic respiratory
  symptoms, including chronic cough, wheezing, or poor exercise
• Meconium ileus, caused by thick inspissated meconium is a
  common presentation in the neonatal period.
• Failure to thrive, as pancreatic insufficiency increases, is a
  common presentation in infancy and childhood.
• Neonatal screening for CF is currently available in all 50 states.
• In patients with suspected CF who have not received neonatal
  screening, a sweat chloride test is commonly performed, which
  often shows high concentrations of chloride and sodium within
  sweat. A concentration in sweat of greater than 60 mmol/L is
  considered diagnostic of CF.

                                   Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient
                                   Registry Annual Report 2000. Bethesda: Cystic Fibrosis
                                   Foundation, 2001.
       Affected Organs in CF
• Sinuses – Sinusitis, nasal polyps
• Lung – Endobronchitis, bronchiectasis
• Pancreas – Exocrine Insufficiency
             CF Related Diabetes
• Intestine – Meconium ileus
• Liver –Sclerosis
• Vas Deferens – failure to develop
• Sweat gland – salt-losing dehydration
                                      Welsh and Smith, Sci Am, 1995
CF Lung Disease
End-stage Lung Disease in CF
          Current Treatments
• Antibiotic therapy, airway clearance
• The clearance of mucus and inflammatory debris from
  the airways will help improve the patient’s lung
• Airway clearance therapy CPT, Flutter®, Acapella®,
  Vest®, IPV
• Nebulized hypertonic saline, which will induce the
  expectoration of mucus.
• Dornase alfa to decrease the viscosity of purulent
  sputum and to help relieve mucus plugging
• Patients will receive mechanical airway clearance
  treatment, such as manual chest physiotherapy,
  autogenic drainage with forced expirations, and high-
  frequency oscillating vest therapy
• Supplementation of the fat-soluble vitamins (vitamins
  A, D, E, and K.
Effects of a short-term rehabilitation program on
   airway inflammation in children with cystic
• Investigated the effects of pulmonary rehabilitation,
  including physical activity and chest physiotherapy, on
  airway inflammation in children with CF.
• Eighteen children with stable CF (six females), aged 8.2-
  16.2 years, participating in a 3-week multidisciplinary
  inpatient rehabilitation program were recruited.
• Median (IQR) symptom scores decreased from 19 [23] to
  16 [21], P = 0.005.
• Vital capacity and FVC increased significantly (P < 0.05).
• Short-term inpatient rehabilitation for children with stable
  CF with intensive physical activity mainly improve
  subjective clinical symptoms and measures of lung
  function such as VC and FVC
                                  Moeller A, et al. Pediatr Pulmonol. 2010 Jun;45(6):541-51.
 Trampoline use as physiotherapy
    for cystic fibrosis patients.

• Papers in the general pediatric population mostly document
  an increased incidence of injuries, ranging from minor
  trauma to spinal cord injuries and even death
• Based on the accumulated data, the presumed benefits of
  trampoline use for CF patients are not proven.
• The suggested benefits could be acquired using other types
  of exercise. Weighing the known risks of trampolines
  against the potential benefits that are not unique to this
  modality suggests that the use of trampolines for CF
  should not be recommended.

                                        Barak A, et al. Pediatr Pulmonol. 2005
           Usefulness of a program of hospital-
    supervised physical training in patients with cystic

• Evaluation of the effects of a physical aerobic training
• Cystic fibrosis patients participated in 12 weeks of training
  twice a week. Each training session consisted of walking
  or running on the treadmill for 30 min at the speed that
  allowed the child to attain 60% of the maximal heart rate
  obtained during a baseline stress test for 4 weeks, 70% in
  the following 4 weeks, and 80% in the last 4 weeks, under
  strict medical supervision.
• There was a significant increase in time of exercise (TE) (P
  < 0.002), VO2, VO2/kg, and pulmonary ventilation (VE)
  (P < 0.0001, P < 0.001, and P < 0.001, respectively).
• A simple training program improves short-term
  cardiopulmonary fitness in children with CF
                                Turchetta A, et al. Pediatr Pulmonol. 2004 Aug;38(2):115-8.
Effect of Exercise on lung function
in children with cystic fibrosis.
• Cystic fibrosis (CF) lung disease leads to progressive
  deterioration in exercise capacity.
• Lung function, nutritional status, and exercise capacity and
  assessments of habitual activity were measured before and
  after a two-month, subject-designed exercise regimen
  based on self-reported activity assessment
• Subjects completing the study demonstrated significant
  improvement in exercise capacity and body image
  perception, a CF-specific QoL measure (p<0.001).
• In secondary analyses, subjects improving exercise
  capacity showed significant increases in lung function and
  self-reported habitual activity.
                                            Paranjape SM, et al. Cyst Fibros. 2012

The substitution of valine for glutamic acid in beta-
globulin of hemoglobin has been known as the
cause of sickle cell anemia since 1957. That this
specific knowledge has not resulted in a rationally
designed, specific cure is a disappointment.
               Platt, OS. NEJM 2000;342:1904-1907
         Sickle Cell Disease
           Clinical Background
• 1:650 African Americans
• 70-80,000 patients in US
• Median Life Expectancy
  – 48 years in females; 42 years in males
• Improved Pediatric Survival
  – Newborn Screening
  – PCN prophylaxis
  – Pneumococcal and HIB vaccine
Derangements Affecting the Lungs in HbSS Disease

• Right shift of the oxygen- Hb                   • Increased synthesis of reactive
  dissociation curve ----- hypoxemia.                oxidants --- tissue injury
• Hypercoaguability ----- increased thrombin,
  fibrin, and platelet activation.                • Functional asplenia – deficient
• Arteriolar vasculopathy – adherence of red blood
  cells to vascular endothelium.

                           Bunn HF, N Engl J Med 1997; 337:762-69.
 Acute Sickle Cell Pneumopathies

• Vasocclusive (pain) crises with splinting
  and resultant atelectasis
• Asthma Exacerbations
• Asthma Exacerbations preceding pain crises

• Acute Chest Syndrome
 Acute Sickle Cell Pneumopathies

Vasocclusive crisis with atelectasis
  • Painful involvement of ribs, sternum, spine
    or abdomen
  • Splinting with reduced ventilation
  • Segmental or lobar atelectasis
  • Increased V/Q mismatch, alveolar hypoxia
    and intrapulmonary shunting
     • ? Prelude to Acute Chest Syndrome (ACS)
Sickle Cell and Airway Reactivity

• Chronic airway inflammation likely

• Studied by cold-air challenge
  – “Hyperreactivity” noted
     • 73% prevalence in group
     • 64% in “asymptomatic” subgroup
                         Allen, J Ped 1997; 131:278-83
       Pulmonary Function in Children with
               Sickle Cell Disease

• 63 children and adolescents
  – 35 African Americans and 28 Hispanics
  – homozygous SS disease
• 35% with lower airway obstruction
  – 78% respond to bronchodilator
• 8% with restrictive disease
  – 67% respond to bronchodilator
                             Koumbourlis et al. J Peds 2001
The Asthma Phenotype and Acute Chest
• Asthma and increased bronchial hyper-reactivity but
  not atopy are more common in children with SCD
  than age and ethnically matched controls
• SCD Children with Atopy and Asthma (“Atopic
  Asthma”) are more likely to have recurrent ACS

• Asthma is associated with increased risk for both
                  Knight-Madden JM et al Thorax 2005;60:206-210

    ACS and CVA

                   Nordness ME et al. Clin Mol Allergy 2005;3:2-6
Acute Chest Syndrome - ACS
 • Acute Pulmonary Illness in Patient with SCD
    – Up to 50% initially admitted for another dx
                             Vichinsky, NEJM 2000;342:1855-65

 • Accounts for 25% of deaths in SCD
    – Most common cause of death in SCD
 • More Common in Children
    – 50% of children with SCD in first decade
                             Gill, Blood 1995; 86:776-783

 • Most Prevalent in SS Disease
    > SC > S-Thalasemia
• 50% of patients originally admitted for VOC
• New Pulmonary Infiltrates
    – Initial CXR may be normal
•   Fever (83%)
•   Cough (65%)
•   Chest Pain (41%)
•   Tachypnea (47%)
•   Dyspnea (35%)
•   Mean SpO2 92%
                    Vichinsky NEJM; 2000;342:1855-1865
        Keys to Therapy
•   Early recognition
•   Adequate pain control
•   Adequate hydration, correction of acidosis
•   Antibiotics
    – cephalosporin & macrolide
• Hematologic Support
    – Simple Transfusion
        • Elevate Hb to 10-12g/dl
        • Elevate HbA %
    – Exchange Transfusion
        • Reduction in HbS% - <30%
       Inpatient Management of ACS at
       Children’s Healthcare of Atlanta
• Pulmonology consultation in any patient with VOC and altered
  pulmonary mechanics, atelectasis or hypoxemia.
• Early management of ACS
   – Aggressive pain control
   – Adequate hydration
   – Supplemental oxygen
   – Bronchodilator therapy
   – Incentive Spirometry / PEP therapy/ VEST therapy
   – Non-invasive ventilation with moderate dyspnea, increasing hypoxemia O2
     requirement > 2 lpm
   – Simple transfusion
   – Ceftriaxone + macrolide
  • Adequate oxygenation
     • Maintain SpO2 93%-95%
  • Adequate pulmonary toilet
     •   ?CPT
     •   segmental breathing, “huff breaths”
     •   Vest therapy
     •   Bronchoscopy/Mucolytics
  • Adequate ventilation
     • Incentive spirometry (Bellet, NEJM 1995;333:699)
     • Non-invasive vs. invasive ventilation
     Other Therapies
     • Steroids
     • ECMO
     • iNO
                VEST THERAPY
• High frequency oscillatory chest percussion
• Well tolerated in patients with pain
• Multiple vest sizes
• Alternative or adjunct to CPT, airway
  clearance techniques
• Decreases atelectasis, facilitates recruitment
• Settings
    – 7 to 12 Hz (1-20)
    – Pressure level 5-7 (1-15)
    – 10 minute cycles x 2-3 up to qid
Non-invasive Ventilation in Acute
       Chest Syndrome
• Early intervention to prevent or slow
  pulmonary deterioration
• Facilitates alveolar recruitment Decreases
  hypoventilation due to pain and resultant
• Decreases atelectasis
• Improves V/Q matching, decreases alveolar
 Chronic Pulmonary Problems
and Management of the Patient
   with Sickle Cell Disease
   Comprehensive Sickle Cell Pulmonary
• Each patient jointly seen by hematologist and
• Full pulmonary function, oximetry at each visit
• Continuous database
• Inhalation technique review (spacer teaching)
• Ongoing therapy
• Social services support
     Proactive Cardiopulmonary
• Diagnostics
  – Serial Pulmonary Function Testing
     • Spirometry
     • Plethysmography
     • DLCO
  – Polysomnography
  – Routine Pulse Oximetry
  – Echocardiogram
        Pulmonary Function Testing
• Identification of Increased Airway Reactivity
   – bronchodilator response
• Identification of Obstructive Disease
• Identification of Restrictive Disease
• Serial measurement of DLCO/VA
   – normal early
   – rises in early teen years
      • correction for anemia, alveolar volume
   – normalizaltion may suggest “shrinking” pulmonary
     vascular bed
Management of Obstructive Lung Disease
       in Sickle Cell Disease
• Surveillance
  – Serial Spirometry and Plethysmography
• Management
  – Maintenance Anti-Inflamatory or Combination Therapy
     • ICS, LTRAs
     • ICS+LABAs
  – Prn Bronchodilators, Exercise Pre-treatment
  – Routine Pneumoccocal and Influenza Vaccines
            Monitoring of Restrictive Lung
            Disease in Sickle Cell Disease
•    Surveillance
    –   Serial Spirometry, Plethysmography, DLCO
    –   Polysomnograpy or 24 hr Oximetry
    –   Echocardiograpy
•    Management
    –    Supplemental Nocturnal Oxygen (if indicated)
    –    Trial of Inhaled Therapy
        • ICS or Combination Therapy
        • Prn Bronchodilators
    –    Consider Hydroxyurea
    –    ? 5-Lipoxygenase Inhibitors
         Management of Restrictive Lung
          Disease in Sickle Cell Disease
• Management
  – Pulmonary Recruitment Therapy
     •   Incentive Spirometry
     •   PEP Therapy
     •   VEST Therapy
     •   Nocturnal BiPaP
  – Routine Influenza and Pneumococcal Vaccines
  – Treatment of Pulmonary Hypertension (if present)
  – Consideration of Hydroxyurea
   Sickle Cell Disease(SCD) and Nocturnal
    Oxyhemoglobin Desaturation (NOD)
• Nocturnal desaturation seen in up to 40 % of children and
  adolescents with SCD
                           Franco M, ARCCM 1996;153:A496
• OSA may be more severe and may complicate SCD
                           Sidman 1986, Madden 1988, Samuels 1992
• OSA does not appear to explain the prevalence of NOD
                           Brooks 1997, Needleman 1999
• Reduced pulmonary function does not correlate with NOD
                           Needleman 1999
• V/Q mismatching which may result from progressive sub-clinical
  intrinsic lung disease not systematically explored
Management of Nocturnal Hypoxemia in Children
           with Sickle Cell Disease

• Surveillance
  – Serial Oximetry
  – Consider polysomnography in any child with SaO2 <
    93%, history of ACS or suspected lung disease
  – Echocardiography
      Management of Nocturnal Hypoxemia in
        Children with Sickle Cell Disease
• Management
  – Treatment of any Obstructive Sleep Apnea (OSA)
  – Supplement for TST (total sleep time)< 90% > 10%
  – Titrate oxygen supplementation to maintain nocturnal SaO2 > 93%
  – Repeat polysomnography or home surveillance of nocturnal
  – Sprometry, Plethysmography, DLCO when possible
  – Aggressive management of clinically or physiologically evident
    lung disease
                PAH in Sickle Cell Disease

32%     frequency of PAH in adult patients with SCD
      –N=195; Hb SS (69%), SC (18%), S-Thal (12%)
      –Increased risk of death (rate ratio 10.1, 95%CI 2.2 to 47.0, P<0.001)

Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death
in patients with sickle cell disease. N Engl J Med 2004;350:886–95.
                 Age and PAH in Sickle Cell Disease

Above  patients <20 y.o. all 18 y.o.
Other studies published in abstract form estimate PAH prevalence of 25% in children
 with SCD and as high as 57% in the setting of comorbid pulmonary problems1
8-33%    prevalence in children from other studies2
    1 - Castro O, Gladwin M. Pulmonary Hypertension in Sickle Cell Disease. Hem Onc Clin Nor Am. Vol 19, 2005.
    2 - J Pediatr Hematol Oncol. 2009 Feb;31(2):97-100. Pediatr Pulmonol. 2009 Mar;44(3):281-9.
           Contributing factors
• Hemolysis
   –   Markers of hemolysis correlate with PH
   –   NO scavenging by free Hb
   –   Oxidative stress (reactive O2 and NO species)
   –   Erythrocyte arginase release
   –   Downstream effects
        • VCAM-1, P-selectin, endothelin-1, thrombosis
• Acute chest syndrome, pneumonia, chronic
  hypoxemia, other pulmonary disease
• Endothelial damage from sickling, in situ
• Other – iron deposition, liver disease,
  hyposplenism, anemia, high cardiac output
 Etiologic Considerations As A Basis
         for Therapy in PAH
• Elevated pulmonary artery pressures (i.e.
  MPAP>25 mmHg)
  – Due to left heart disease
    •   Normal transpulmonary gradient
    •   PVR < 3 indexed WU
    •   Elevated PCWP or LVEDP
    •   Diuretics, ACE-inhibitors, beta-blockers
  – Due to increased PVR
    • Elevated transpulmonary gradient and PVR
    • Normal or mildly elevated PCWP or LVEDP
    • Pulmonary vasodilators, warfarin
  – Mixed etiology
    • Moderately+ elevated PCWP/LVEDP
    • PVR > 3 indexed WU
    • Treat left-heart disease first, re-evaluate after 6 months
  Prevalence and Risk Factors of Elevated Pulmonary Artery
         Pressures in Children with Sickle Cell Disease
            Pashankar, FD et al. Pediatrics 2008;121(4):777-782

• Echocardiography obtained in 62 patients with SS or S0
  thalassemia 6 years or older in outpatient setting
• 30 % (19/62) with TR > 2.5 m/sec consistent with PAPest > 30 mm
• Elevated PAP observed only in SS patients
• Unrelated to age or gender
• Elevated PAP associated with
   – Higher reticulocyte count ( p = .01)
   – Higher platelet count (p = .03)
   – Lower SpO2 (p = .03)
• 13 % (8/62) with a history of CVA or abnormal TCD
   – No elevation of PAPest observed
    Monitoring at Children’s Healthcare of Atlanta

• Screen starting at age 5 years
• TR jet < 2.5 m/sec
    –   Screening echo every year
    –   TR jet 2.5-3 m/sec
    –   Confirmatory repeat echo within 6 mo
    –   If still 2.5-3 m/s, consider intensification of sickle cell treatment
          • Hydroxyurea, chronic transfusion
          • Aggressive pulmonary management
    – Identify and optimize contributing factors
          • OSA (T & A, CPAP/BiPaP, O2), iron overload (chelation), thromboembolism
          • Q6 mo echo while in this range
• TR jet > 3 m/sec
    – Confirmatory repeat echo within 3 mo with cardiac evaluation
    – Same recommendations as above for 2.5-3 m/sec plus
    – If TR jet is still >3 m/s, consider right heart catheterization in discussion
      with hematology (sedation/transfusion recommendations from hematology
      prior to procedure)
          • Left heart disease vs PVD vs mixed
     Pulmonary Vasodilator Therapy for PAH in SCD

  • Choice based on relative risk profile for individual
  • Sildenafil (Revatio, Viagra) - safe in small series of patients in open
    label use1
     – PDE-5 inhibitor, increases NO levels
     – Rationale: impaired NO synthesis due to increased arginase activity;
       increase NO destruction via free hemoglobin scavenging
     – Risks: priapism
  • (Bosentan (Tracleer) – currently in trial for this indication
     – Nonspecific endothelin receptor antagonist
     – Rationale: elevated endothelin levels in SCD, pulmonary vascular
     – Risks: liver toxicity, anemia, increases plasma volume
  • L-arginine? (low toxicity, minimal evidence, fair rationale)

1 - MachadoRT, Martyr SE, Anthi A, et al. Pulmonary hypertension in sickle cell disease…. Br J Haematol 2005;130:445–53.
  Derchi G, Forni GL, Formisano F, et al. Efficacy and safety of sildenafil…. Haematologica 2005;90:452–8.
       ?Potential Reduction in SCLD
• Increases HbF, decreases HbS%, ?decreases
• Significant reduction in ACS in adults and
           Marwick, JAMA 1995;273:611, Scott J Ped 1996;128:820

• Decrease in VLA-4 and CD36 adhesion
           Styles, Blood 1997;89:2554

• Splenic regeneration
           Claster, Blood 1996;88:1951

  Hydroxyurea may be an NO donor
   Spectrum of pulmonary problems
Exercise                 PA hypertension            •Low pO2
                                                    •Low NO
                          Chronic Lung              inflammatory
                          Disease                   mediators
                                                    •High VCAM
                         Acute Chest

                                                  Non ACS Vaso-
Asthma                                     Pain   occlusion
          2012 American Thoracic
           Society - Multi-Center
         Collaboration to Establish:
• Pediatric Sickle Cell Registry
   – Epidemiological Data Base
   – Monitoring
• Controlled Clinical Trials
   – Chronic Pulmonary Management
      • Application of traditional therapies
      • Application of novel therapies
          – Anti-inflamatory
          – Cytoprotective
   – Acute Chest Syndrome Management
      • Application of traditional therapies
      • Application of novel therapies
Pediatric Neuromuscular Syndromes
• Neuromuscular diseases are disorders caused by
  an abnormality of any component of the lower
  motor neuron system: anterior horn cell,
  peripheral nerve, neuromuscular junction, or
• Acquired - poliomyelitis, Guillain-Barré
  syndrome, myasthenia gravis, polymyositis
• Genetic - spinal muscular atrophy, hereditary
  motor sensory neuropathy, congenital myasthenia
  gravis and Duchenne's muscular dystrophy
                Cuccurullo S. Physical Medicine and Rehabilitation Board Review. Neuromuscul
                Disease in Children
           Common symptoms
•   infantile floppiness or hypotonia
•   delay in motor milestones
•   feeding and respiratory difficulties,
•   abnormal gait characteristics, frequent falls,
    difficulty with stairs or arising from the

                            Cuccurullo S. Physical Medicine and Rehabilitation Board
                            Review. Neuromuscular Disease in Children
        Physical Exam Findings
• Pseudohypertrophy - Increased gastrocnemius calf
  circumference caused by increase in fat and connective
  tissue, not true muscle (DMD, Becker’s)
• Stork leg appearance—focal atrophy of distal lower
  extremity muscles particularly seen in hereditary motor
  sensory neuropathy
• Muscle fasciculations—seen in a variety of lower motor
  neuron disorders, especially common in spinal muscular
• Hepatosplenomegaly—common in metabolic myopathy
  such as acid maltase deficiency and types 3 and 4

                              Cuccurullo S. Physical Medicine and Rehabilitation Board
                              Review. Neuromuscular Disease in Children
           Physical Exam Findings
• Gowers' sign—results from proximal weakness of the pelvic girdle
  muscles causing patients to rise off the floor assuming a four-point
  stance on hands and knees,

• Toe walking/myopathic gait—weakness of hip extensors produces
  anterior pelvic tilt and tendency for trunk to be positioned anteriorly to
  the hip. Patients compensate by maintaining lumbar lordosis, which
  positions their center of gravity posterior to the hip, stabilizing the hip
  in extension.

• Trendelenburg gait/gluteus medius gait—weakness of hip abductors
  produces tendency toward lateral pelvic tilt and pelvic drop of swing
  phase side. Patient compensates by bending the trunk laterally over the
  stance hip joint

• Steppage gait/foot slap—occurs secondary to distal weakness affecting
  ankle dorsiflexion and evertors. Steppage gait facilitates clearance of
  plantar flexed ankle
                                       Cuccurullo S. Physical Medicine and Rehabilitation Board
                                       Review. Neuromuscular Disease in Children
            Dystrophic Myopathies
• Duchenne’s and Becker’s Muscular Dystrophy
• Early on weakness is generalized, however, predominantly
• Greater than 40%–50% loss of muscle power occurs by age 6
  years. The average age to wheelchair dependency is
  approximately 10 years with a range of 7–13 years.
• Scoliosis—Prevalence varies from 33%–100% and is related to
  age. 50% acquire scoliosis between ages 12–15 years.
• Pulmonary—Forced Vital Capacity (FVC) volumes increase
  during the first decade of life and plateau during early part of the
  second decade. There is a linear decline of FVC between age 10
  and 20. FVC less than 40% is a contraindication to surgical spinal
  arthrodesis secondary to increased peri-operative morbidity
• Cardiomyopathy usually is first noticed at age greater than 10
  years and is apparent in nearly all patients more than 18 years old.
                                   Cuccurullo S. Physical Medicine and Rehabilitation Board
                                   Review. Neuromuscular Disease in Children
     Management of Dystrophic
• Promotion of activity
• Prevention of fixed deformity (e.g.,
  equinus) by passive stretching
• Braces for promotion of ambulation if
  loss of ability to walk in late stages
  Prevention and management of
  scoliosis if chairbound
 Therapy in Neuromuscular Disease
• Eccentric or lengthening contractions produces more
  mechanical stress on muscle fibers than concentric or
  shortening contractions
• No systemic studies using Duchenne's muscular dystrophy
  populations have shown any deleterious effect of
  resistance exercise. Generally a submaximal strengthening
  program is prescribed
• Wheelchair reliance is imminent when knee extension
  strength becomes less than anti-gravity and time to
  ambulate 30 feet is greater than 12 seconds
• Duration of ambulation in Duchenne's muscular dystrophy
  has been successfully prolonged by 2 to 5 years by prompt
  surgery and bracing following loss of independent
• Little evidence supports the efficacy of early prophylactic
  lower extremity surgery in Duchenne's muscular dystrophy
  for independently producing prolonged ambulation
     •Cuccurullo S. Physical Medicine and Rehabilitation Board Review. Neuromuscular Disease in Children
Congenital Muscular Dystrophies
• A heterogeneous group of cases presenting with clinical
  weakness or deformities in early infancy and having
  variable dystrophic changes in the muscle
• Presenting with hypotonia and weakness, fixed deformities
  (arthrogryposis), variable sucking, swallowing, and
  respiratory difficulty, delayed motor milestones in later
  onset cases
• Variable course and prognosis
• Infants present with hypotonia, muscle weakness at birth
  or within the first few months of life, congenital
  contractures and a dystrophic pattern on muscle biopsy
• Children exhibit early contractures, equinovarus
  deformities, knee flexion contractures, hip flexion
  contractures and tightness of wrist flexors and long finger
                                Cuccurullo S. Physical Medicine and Rehabilitation Board
                                              Review. Neuromuscular Disease in Children
• Active physiotherapy to encourage mobility
• Passive stretching of "fixed" deformities
• Surgical correction of residual deformities at
  appropriate stage (equinovarus correction when
  able to stand)
• Avoid immobilization that promotes fixed
• Supportive treatment for respiratory problems

                          Cuccurullo S. Physical Medicine and Rehabilitation Board
                          Review. Neuromuscular Disease in Children
       Spinal Muscular Atrophy
SMA Type I (Werdnig-Hoffman Disease)—Severe SMA
• An autosomal recessive disorder of early infancy with
  severe axial and limb weakness due to degeneration of the
  anterior horn cell of the spinal cord
• Presents in the first months of life with hypotonia and
  weakness, sucking and swallowing difficulty, respiratory
• Cardinal Clinical Signs - severe limb and axial weakness,
  frog posture, marked hypotonia, poor head control, bell-
  shaped chest
• Prone to respiratory infections
• Prognosis poor; majority die of pneumonia in first year,
  most within 3 years
• Fasciculation of tongue (about 70%)
                         •Cuccurullo S. Physical Medicine and Rehabilitation Board Review.
                         •Neuromuscular Disease in Children
          SMA – Type II
• Intermediate SMA
• weakness predominantly of the
  legs, with ability to sit unsupported
  but not to stand, due to
  degeneration of the anterior horn
  cells of the spinal cord
• Presents between 6 and 12 months
                •Cuccurullo S. Physical Medicine and Rehabilitation Board Review.
                •Neuromuscular Disease in Children
• Prevention of scoliosis by early bracing
• Treatment of scoliosis by spinal braces or
• Early achievement of standing posture in
  standing frame or calipers
• Promotion of ambulation by appropriate

                    •Cuccurullo S. Physical Medicine and Rehabilitation Board Review.
                    •Neuromuscular Disease in Children
                 SMA Type III
• SMA Type III (Kugelberg-Welander syndrome)
• Mild SMA characterized by proximal weakness,
  predominantly of the legs, due to degeneration of the
  anterior horn cells of the spinal cord
• Presents from the second year of life through childhood
  and adolescence into adulthood
• Presents with difficulty with activities such as running,
  climbing steps, or jumping, abnormal gait; waddling, flat-
  footed, wide base
• Difficulty rising from floor (Gowers' sign), proximal
  weakness; legs > arms
• Hand tremor (variable), Tongue fasciculation (variable)
• Good long-term survival, depending on respiratory

                          •Cuccurullo S. Physical Medicine and Rehabilitation Board Review.
                          • Neuromuscular Disease in Children
• Encourage activity and
• Rehabilitation in braces if
  ambulation lost
• Vigorous treatment of
  respiratory infections
                Cuccurullo S. Physical Medicine and Rehabilitation Board
                Review. Neuromuscular Disease in Children

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