Acute Respiratory Illnesses in Children

Acute Respiratory Illnesses in Children

Derek Zhorne, MDClinical Assistant Professor of Pediatrics

Pediatric Hospitalist

Disclosures

I have no actual or potential conflicts in relation to this presentation.

I will be referring to some industry products in regards to non-invasive respiratory support options for pediatric patients.

Objectives

Discuss the diagnostic evaluation and management of bronchiolitis & community-acquired pneumonia

Discuss non-invasive respiratory support for these conditions

Review some of the commonly encountered diagnostic & therapeutic dilemmas

Bronchiolitis

▪ Most common cause of hospitalization among infants during the 1st year of life

▪ 1 in 5 infants of each birth year cohort require outpatient medical attention during the first year of life for RSV

▪ ~ 100,000 bronchiolitis

admissions / year in

the US for estimated

cost of $1.73 billion

https://www.morethanacold.co.uk/Illustration by: Hélène Desputeaux

Bronchiolitis – Clinical Features

“A young child (0 – 18 months old) with

bronchiolitis typically presents during the winter

months after 2-4 days of low-grade fever, nasal

congestion, rhinorrhea and sxs of lower respiratory

tract infection as manifested by grunting, nasal

flaring, intercostal / subcostal / supraclavicular

retractions, inspiratory crackles and expiratory

wheezing.”

- NEJM 2016

Bronchiolitis – Pathophysiology

ReferenceRossi GA, Silvestri M, Colin AA. Viral Bronchiolitis in Children. N Engl J Med. 2016;374(18):1792-3

Bronchiolitis - Microbiology

▪ Many viruses that infect the respiratory system cause

similar signs and symptoms

▪ Seasonality of viral infections is relevant

Virus Frequency (%)

Respiratory Syncytial Virus 50-80

Human rhinovirus 5-25

Parainfluenza virus 5-25

Human metapneumovirus 5-10

Coronavirus 5-10

Adenovirus 5-10

Influenza virus 1-5

Enterovirus 1-5

Bronchiolitis – Microbiology

▪ nucleic acid amplification tests ↑ detection of viruses…

▪ “co-infections” with multiple viruses are frequently seen

Studies have shown that at least 1 respiratory virus

can be found in up to 30% of children < 6 years old who

have no respiratory symptoms.

1) Asymptomatic colonization

2) Incubation before clinical infection

3) Prolonged viral shedding post-infection

Bronchiolitis – RSV

▪ Enveloped single-stranded RNA virus of the

Paramyxoviridae family.

▪ RSV reinfection occurs throughout life, despite induction

of both antibody and T-cell responses after primary

infection

▪ Poor understanding of the mechanisms limiting the

induction of long-lasting immunity has delayed the

development of an effective vaccine

Bronchiolitis – Clinical Course

▪ Variable and dynamic

▪ Proper assessment requires serial exams over a

period of observation – after nasal suctioning

ReferenceFlorin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet. 2017;389(10065):211-24.

Bronchiolitis – High Risk Patients

▪ Infants <3 months old

▪ Hx of prematurity (<32 weeks)

▪ Chronic Lung Disease

▪ Immunodeficiency

▪ Congenital Heart Disease

▪ Neuromuscular Disorders

Apnea in Bronchiolitis

▪ Apnea is a life-threatening complication of bronchiolitis

▪ Incidence of apnea has varied from 1-24% in different studies

Retrospective cohort study of ~700 infants hospitalized with bronchiolitis

• Inpatient apnea identified in 19 patients (2.7%, 95% CI: 1.7 - 4.3%)

All patients who had apnea were identified by the following 3 “high-risk” criteria:

1. Born full-term (≥ 37 weeks) and currently < 1 month old

2. Born preterm (<37 weeks) and < 50 weeks postmenstrual age

3. Child’s parents or a clinician had witnessed apnea before admission

ReferenceWillwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med. 2006;48(4):441-7.

Caffeine for the Treatment of Apnea in

Bronchiolitis?

A Cochrane review and meta-analysis of 6 RCTs showed that methylxanthines (i.e., theophylline or caffeine)

are effective in treating apnea of prematurity

▪ ↓ # of apnea events

▪ ↓ need for mechanical ventilation

Proposed mechanism of action

- increased central respiratory drive

- increasing chemoreceptor sensitivity to carbon dioxide

- improved skeletal muscle contraction

Assessment:

Single center RCT enrolled 90 infants diagnosed with viral bronchiolitis who presented to a pediatric ER with

history of apnea or observed apnea

Patient: Infants ≤ 4 months old with bronchiolitis

Intervention: IV dose of caffeine (25 mg/kg in 15 ml D5W)

Comparison: 15 ml normal saline

Outcome(s): time until a 24-hour apnea-free period

Mean duration to a 24-hour apnea-free period was 28.1 hrs (caffeine group) vs. 29.1 hours (placebo group).

Recommendation

A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis

NNT = 452

ReferenceAlansari K, Toaimah FH, Khalafalla H, El Tatawy LA, Davidson BL, Ahmed W. Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial. J Pediatr. 2016;177:204-11.e3.

Bronchiolitis – Supportive Therapies

No available treatment shortens the

course of bronchiolitis or hastens the

resolution of symptoms


NOT Recommended

• short-acting β2-agonists

• racemic epinephrine

• systemic glucocorticoids

• ribavirin

• chest physiotherapy

• antibiotics

• Testing for viral causes*

• Chest X-ray*

2014 AAP

Clinical Practice Guideline

• Nasal saline drops and suctioning

• Supplemental oxygen to keep SpO2 >90%

• IV or NG fluids if unable to maintain hydration orally

• May consider nebulized hypertonic saline if hospitalized (RCTs with inconsistent findings)


Standard Nasal Cannula (“Low Flow”)

• 100% oxygen through bubbler humidifier at rate of 0 – 4 LPM

• FiO2 varies from 25-40% depending on RR, TV and extent of mouth breathing

• Flow > 2 LPM is irritating to nares unless heated & humidified

Heated, Humidified High Flow Nasal Cannula (HFNC)

• Heated and humidified oxygen via special devices at rates up to 8 LPM in infants and 60 LPM in adults

• Better tolerated than face mask in terms of comfort

• ↓ RR, work of breathing and better oxygenation

High Flow Nasal Cannula

• Provides low-level positive pressure (PEEP) and aids in lung recruitment

• Provides CO2 “washout” of respiratory physiologic dead space

• Warmth and humidity keep secretions moist and improve mucociliary clearance

RAM Cannula & CPAP

• Designed by neonatologist for use in premies as

alternative to nasal CPAP

• Has softer, thinner walled prongs with larger nasal prong

inner diameter → results in lower airflow resistance with

reduced nasal trauma

Complications of HFNC or RAM CPAP

Nasal irritation

Abdominal distension

Pneumothorax

Community-Acquired Pneumonia

Does this child have pneumonia?

Case 1

18 month old male with no significant

PMHx presents to PCP with 1 day

history of fever and cough. Parents

report decreased PO intake for past

24 hours. Attends daycare.

Vital Signs: Temp 38.5°C, RR 48,

SpO2 93% on room air

Exam: Awake, alert with no signs of

respiratory distress. He has diffuse

crackles (R > L) with no wheezes.

Other findings from his exam are

normal.

Case 2

2 year old female with no significant

PMHx presents to PCP with 4 days of

fever and cough. Parents report

decreased PO intake for the past 24

hours and they have noticed difficulty

breathing. Attends daycare.




respiratory distress. She has

crackles in right lower posterior chest.

Other findings from her examination

are normal.

Community-Acquired Pneumonia (CAP)

• Pneumonia is the single greatest cause of death in children worldwide

• In the developed world, the annual incidence of pneumonia is ~3-4 cases per 100 children <5 years old

• There is no universally accepted and practical reference standard for diagnosis of pediatric CAP

ReferenceWalker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):1405-16.

CAP - Diagnosis

Depends on who you ask

World Health Organization (WHO)

British Thoracic Society Infectious Disease Society of America (IDSA)

Cough or difficulty breathing and age-adjusted tachypnea

2 – 11 mo: RR ≥ 50 1 – 5 yo: RR ≥ 40 ≥ 5 yo: RR ≥ 20

Persistent or repetitive fever > 38.5 or 101.3 with chest retractions and increased respiratory rate

Presence of signs and symptoms of pneumonia in a previously healthy child caused by an infection that has been acquired outside the hospital

CAP – Clinical Features

CharacteristicFrequency in children with radiographic evidence of

pneumonia

Symptom

Cough 95%

Abnormal temperature

91%

Anorexia 75%

Dyspnea 70%

Chest wall retractions

55%

Radiographic Findings

Consolidation 58%

Alveolar or interstitial infiltrate

51%

Pleural effusion 13%

Adapted from Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. NEJM2015;372(9).

• Signs / Symptoms

– Fever

– Cough

– Tachypnea

– Dyspnea

– Chest pain (adolescents)

– Abdominal pain

– Crackles / Rales

– Diminished breath sounds

– Wheezing

– Grunting (infants)

– Nasal flaring

– Chest wall retractions (infants)

– Hypoxemia

CAP - Pathophysiology

Anatomic & Mechanical Barriers

- Upper respiratory tract nasal hairs & turbinate architecture to trap particles

- Mucociliary clearance of secretions

- Epiglottic reflex to prevent aspiration and cough to expel things that may be aspirated

- Complex respiratory airway branching

Humoral Immunity

- Secretory IgA is major immunoglobulin produced in upper airways and has antibacterial / antiviral activity

- IgG and IgM enter airways via transudation from blood and opsonize bacteria, activate complement and neutralize toxins.

Phagocytic Cells

- Alveolar macrophages are first line of cellular defense.

- Interstitial macrophages

- Intravascular macrophages

Cell-Mediated Immunity

- Lymphocytes play critical role in producing antibodies, cytotoxic activity and cytokine production to fight off viruses and intracellular microorganisms.

PNEUMONIA

Invasion of lower respiratory tract by a pathogenic organism

that alters, inhibits or overwhelms these host defenses

CAP - Microbiology

• Historically, CAP was largely considered a bacterial process– Streptococcus pneumoniae

– Haemophilus influenzae, type b

– Streptococcus pyogenes

– Staphylococcus aureus

• Molecular diagnostics for viral respiratory pathogens have increased awareness of viral causes of CAP

ReferenceJain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. NEJM 2015;372(9).

Vaccines1987 – Hib

2000 – PCV72010 – PCV13

CAP - Microbiology


Community-Acquired Pneumonia Requiring

Hospitalization among U.S. Children


DESIGN:

Prospective population-based surveillance study. Eligible for study if <18 years old and…

1) hospitalized with CAP between Jan 2010 – June 2012

2) resided in 1 of 22 counties which comprised the study catchment areas of participating children’s hospitals (Nashville, Memphis, Salt Lake City)

3) had a CXR performed within 72 hrs before or after admission

RESULTS:

2,638 children were enrolled in the EPIC study.

Of the patients who had both radiographic evidence of pneumonia and blood / respiratory specimens available for bacterial + viral testing…

- Either viral or bacterial pathogen detected 81% cases

- Viral pathogen detected 73% cases

- Bacterial pathogen detected 15% cases

- Both viral + bacterial pathogen detected 7% of cases




Major Findings of the EPIC Study

1. Pathogen (viral or bacteria) was detected in 81% of children– viruses alone were detected in 66% of children

2. Most commonly detected pathogens were viruses– RSV 28%

– Rhinovirus 27%

– Human metapneumovirus 13%

– Adenovirus 11%

3. Typical bacterial accounted for 8% of CAP overall– Streptococcus pneumoniae 5%

– Staphylococcus aureus 1%

– Streptococcus pyogenes 1%

4. Atypical bacteria was much more common in older children– Mycoplasma pneumoniae detected in 19% of children > 5 yo compared to only 3% in

younger children




Children ≤ 4 years old had virus as sole pathogen in ~50% of cases and concurrent viral detection in an additional 15-25% of cases

Etiology of CAP by Age

< 3 months 3 months – 5 years > 5 years

Viral Pathogens

RSV RSV Influenza

Influenza Influenza Adenovirus

Parainfluenza Parainfluenza Human metapneumovirus

Human metapneumovirus Human metapneumovirus Rhinovirus

Bacterial Pathogens

Group B streptococcus Streptococcus pneumoniae Mycoplasma pneumoniae

Gram-negative bacilli Mycoplasma pneumoniae Streptococcus pneumoniae

Streptococcus pneumoniae Staphylococcus aureus Staphylococcus aureus

Bordetella pertussis Streptococcus pyogenes (GAS) Streptococcus pyogenes (GAS)

Chlamydia trachomatis Haemophilus influenza type b Haemophilus influenza type b

Complications Associated with CAP

Pulmonary

Pleural effusion or empyema

Lung abscess

Bronchopleural fistula

Necrotizing pneumonia

Acute respiratory failure

Metastatic Disease

Meningitis

CNS abscess

Pericarditis

Endocarditis

Osteomyelitis

Septic arthritis

Systemic

SIRS → Sepsis

Hemolytic Uremic syndrome

Right upper lobe lung abscess

ReferencePabary R, Balfour-Lynn I. Complicated pneumonia in children. Breathe 2013;9(3)210-222.

Necrotizing Pneumonia a) CXR, Day #1c) CXR, Day #8

ReferencePabary R, Balfour-Lynn I. Complicated pneumonia in children. Breathe 2013;9(3)210-222.

CAP – Viral or Bacterial?

• Significant overlap in clinicalsymptoms

• Typical CXR findings DO NOTdistinguish between viral and bacterial causes

• Acute-phase reactants (ESR, CRP, PCT) cannot be used as sole determinant to distinguish between viral and bacterial causes

CAP – Diagnostic Testing

Recommended Actions

- Pulse oximetry should be performed.

- Obtain respiratory viral testing.

Choose Wisely:

- Do not obtain blood culture in a nontoxic, fully immunized child

- CXR is not necessary at initial visit. Obtain if significant respiratory distress or hypoxemic.

- Blood culture and CBC rarely change treatment course

Outpatient (limited testing)

Recommended Actions

- Pulse oximetry should be performed.

- Obtain respiratory viral testing.

- Blood cultures should be obtained in hospitalized children with moderate-severe CAP

- CBC, ESR, CRP may provide useful information for clinical management.

- CXR (PA + lateral) should be obtained in all hospitalized children with CAP.

Inpatient

CAP – Treatment

In children < 5 yo, the majority of CAP will be due to viral pathogens and no antibiotic treatment is indicated.

1st line Therapy: Amoxicillin x 7 - 10 days

Alternative(s) 2nd / 3rd Gen Cephalosporin

Outpatient

1st line Therapy: Ampicillin

Not fully immunized, severe disease

→ substitute a 3rd Generation Cephalosporin

→ + Vancomycin or Clindamycin if concern for Staphylococcus aureus

Inpatient

What about Mycoplasma pneumoniae?

• Frequent cause of CAP in school-aged children and adolescents

• What does a positive PCR test for Mycoplasma mean?

– The CDC EPIC Study showed Mycoplasma pneumoniae was detected in 8% of children with pneumonia and fewer than 1% of controls

– A cross-sectional, observational study from the Netherlands found higher rates of Mycoplasma pneumoniae in asymptomatic children

• Azithromycin is largely ineffective against other bacterial causes of CAP but is the 2nd most commonly prescribed antibiotic in outpatient pediatrics.

What about Mycoplasma pneumoniae?

• Studies have failed to consistently demonstrate

a benefit of using macrolide therapy in children

with pneumonia.

• However, existing clinical practice guidelines still

recommend macrolide antibiotics for treatment

of children (school-aged and adolescents) in an

outpatient setting. - IDSA 2011

ReferenceKatz SE, Williams DJ. Pediatric Community-Acquired Pneumonia in the United States: Changing Epidemiology, Diagnostic and Therapeutic Challenges, and Areas for Future Research. Infect Dis Clin North Am. 2018;32(1):47-63.

“Secondary” Bacterial Pneumonia

Child with viral URI symptoms.

Begins to show clear clinical improvement.

Abrupt worsening of clinical status.

Bacterial Superinfection

Presence of a preceding viral respiratory tract infection is an important risk

factor in the pathogenesis of bacterial pneumonia.

Chest X-ray*

Public health evidence of this viral-bacterial interplay

-Severe pneumococcal pneumonia has been associated with outbreaks of influenza

-Pneumococcal vaccines decrease the morbidity of influenza infections

Does this child have pneumonia?

Case 1

18 month old male with no significant

PMHx presents to PCP with 1 day

history of fever and cough. Parents

report decreased PO intake for past

24 hours. Attends daycare.




respiratory distress. He has diffuse

crackles (R > L) with no wheezes.

Other findings from his exam are

normal.

Case 2

2 year old female with no significant

PMHx presents to PCP with 4 days of

fever and cough. Parents report

decreased PO intake for the past 24

hours and they have noticed difficulty

breathing. Attends daycare.




respiratory distress. She has

crackles in right lower posterior chest.

Other findings from her examination

are normal. Dx: BronchiolitisNo CXR, no labs. Flu PCR (if winter) Teach family nasal saline / suctioningAnticipatory guidance

Dx: Pneumonia (mild) No CXR, no labs. Flu PCR (if winter) No antibiotics as < 5 yo

Take Home Points

Bronchiolitis

• Influenza testing during appropriate season

• Supportive cares only nasal suctioning fluid hydration supplemental oxygen

• Do not order CXR

• Do not administer albuterol or racemic epinephrine in the office (unless admitting to the hospital)

Community-Acquired Pneumonia

• Limited outpatient evaluation is appropriate for mild disease (pulse ox + respiratory viral testing).

• Viruses > > > Bacteria as cause of CAP in children

• Concerns whether treating Mycoplasma pneumoniae with a macrolide is effective at all

• 1st line treatment should be 7 – 10 days of Amoxicillin

Bibliography

[1] Florin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet. 2017;389(10065):211-24.

[2] Ralston SL, Lieberthal AS, Meissner HC. Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics. 2014;134(5):e1474-e1502. Pediatrics. 2015;136(4):782.

[3] Higdon MM, Le T, O'Brien KL, Murdoch DR, Prosperi C, Baggett HC, et al. Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study. Clin Infect Dis. 2017;64(suppl_3):S378-s86.

[4] Rossi GA, Silvestri M, Colin AA. Viral Bronchiolitis in Children. N Engl J Med. 2016;374(18):1792-3.

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[10] Alansari K, Toaimah FH, Khalafalla H, El Tatawy LA, Davidson BL, Ahmed W. Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial. J Pediatr. 2016;177:204-11.e3.

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[20] Abboud PA, Roth PJ, Skiles CL, Stolfi A, Rowin ME. Predictors of failure in infants with viral bronchiolitis treated with high-flow, high-humidity nasal cannula therapy*. Pediatr Crit Care Med. 2012;13(6):e343-9.

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[23] Schibler A, Pham TM, Dunster KR, Foster K, Barlow A, Gibbons K, et al. Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery. Intensive Care Med. 2011;37(5):847-52.

[24] Mikalsen IB, Davis P, Oymar K. High flow nasal cannula in children: a literature review. Scand J Trauma Resusc Emerg Med. 2016;24(1):93.

[25] Milesi C, Essouri S, Pouyau R, Liet JM, Afanetti M, Portefaix A, et al. High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (TRAMONTANE study). Intensive Care Med. 2017;43(2):209-16.

[26] Franklin D, Babl FE, Schlapbach LJ, Oakley E, Craig S, Neutze J, et al. A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis. N Engl J Med. 2018;378(12):1121-31.

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Acute Respiratory Illnesses in Children

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