Geronimo, Maria Angelica; Geronimo, Ralph Ernesto; Go, Camille-Marie; Go, Crystal Karen January 24, 2011 Pulmonology Conference

General Data J.M. 3 months old Male Race: Filipino Birthday: October 9, 2010 Sampaloc, Manila Roman Catholic Date of Admission: January 12, 2011 Informant: Mother Reliability: 80%

Chief Complaint Difficulty of Breathing

10 days PTA Colds, whitish-yellow discharge; non-productive cough USTH ERCD – suction of secretions – discharged improved and stable 0.65% NaCl Solution (Salinase) 2-3 drops/nostril every 6 hours Erythromycin (3.5 mkd) for 7 days Interval History Persistence of difficulty of breathing, more pronounced on lying down Continue prescribed medications Good suck, good activity 6 days PTA Consulted at USTH-SBC: Acute Nasopharyngitis Continue prescribed medications

CC: Difficulty of Breathing Few hours PTA Persistence of the difficulty of breathing and non productive cough Whitish-yellow nasal secretions No fever, loss in appetite, decrease activity, vomiting ADMISSION

Review of Systems General: (-) weight changes Cutaneous: (-) rashes, (-) jaundice HEENT: (-) eye redness (-) eye discharge (-) ear discharge (-) gum bleeding Cardiovascular: (-) cyanosis Respiratory: see HPI Gastrointestinal: (-) acholic stools

Review of Systems Genitourinary: (-) tea-colored urine (-) oliguria (-) discharge Nervous/Behavior: (-) seizures (-) tremors (-) mood/behavioral changes Endocrine: (-) polyuria (-) polydipsia (-) polyphagia (-) heat/cold intolerance Musculoskeletal: (-) edema (-) swelling (-) limitation of motion (-) tenderness Hematopoietic (-) bleeding tendencies (-) easy bruisability

Gestational History Mother: 36 year-old G1P0 housewife Father:37 year old seaman Regular prenatal checkups USTH OPD for 7 times (-) viral exanthem, radiation and any intake of illicit, prohibited or abortifacient drugs, intake of alcohol and smoking UTI (September 2010) - Cefalexin for 7 days and claimed to be compliant; Repeat UA - normal OGCT and Hepatitis screening were not done

Gestational History Preeclampsia (HBP 160/100; UBP is /70mmHg) Magnesium sulfate Nicardipine drip Betamethasone Emergency CS secondary to preeclampsia

Birth History Live, preterm, singleton male, delivered via “E” CS secondary to preeclampsia BW 1.66 kg BL 44 cm HC 31 cm CC 25 cm AC 22 cm AS 8,9 MT weeks AGA

Neonatal History 1 st hour of life – (+) subcostal retractions - CXR: air bronchogram with densities on the right lower lobe Persistent respiratory distress  intubated (NICU) Ampicillin (51 mkdose) and gentamicin (4mkdose )  meropenem and amikacin (K. pneumonaie) PDA: grade II continuous murmur  furosemide (mkdose?) and Ibuprofen (10mkdose) 2D echocardiography: PDA, patent foramen ovale, LVE, LAE and pulmonary arterial hypertension

Neonatal History 2 nd day of life – jaundice (chest) and hyperbilirubinemia (6.8) Phototherapy on the 5 th HD Neonatal hepatitis Discharged at his 52nd day of life Final Dx: Neonatal sepsis (Klebsiella Pneumonia); PDA and Neonatal Hepatitis

Feeding History Mixed Breastfed and Milk formula 15 minutes/breast 3x a day alternating with Formula S26 lactose free 1 scoop in 2 ounces every 3 hours Mother claims that there is not enough milk being produce that’s why she started on powdered milk Good appetite with no feeding difficulties

24 Hour Food Recall CHOCHONFatsKcal Breakfast Milk 2 ounce64585 Merienda Milk 2 ounce64585 Lunch Milk 4 ounce Merienda Milk 2 ounce64585 Dinner Milk 2 ounce64585 ACI510 RENI560 %91%

Developmental History Good motor activity Visually tracks objects and looks around Has social smile Mother do not practice him to sit with support or do prone position Has head lag when pulled At par with age

Past Medical History October 10, 2010: sepsis, neonatal hepatitis and PDA No previous surgeries done No allergy, eczema, asthma, food or drug sensitivities

Immunization History VaccineDate Hepatitis B 11/22/1012/22/10 BCG11/24/10 DTP12/22/10 OPV12/22/10

Family Profile NameAgeRelationEducational Attainment OccupationHealth SG38FatherCollege graduate SeamanHealthy CG36MotherCollege graduate UnemployedPreeclampsia

Family History (+) Asthma – paternal grandmother (+) HPN – maternal grandmother (-) DM, blood dyscrasia, autoimmune disease, congenital disorders, thyroid diseases, cancer, allergy

Socioeconomic and Environmental History Rented studio type made of concrete Adequate space for each household member, well-lit and well ventilated Water station Meals are home-cooked prepared by his mother or sometimes they buy cooked-meals No pets, no factories or other industrial establishments within the vicinity of the residence Garbage is not segregated and is being collected everyday Not exposed to second hand smoke

Physical Examination Awake, alert, in respiratory distress, ambulatory, well- hydrated, well nourished, ill-looking HR 135 bpm, regular, RR 48 cpm, regular, T36.7 o C, SpO2 91% Wt: 3.26 kg (z score below -3 severely underweight) Lt: 51 cm (z score below -3 severely stunted) BMI: (z score below -2 severely wasted) Warm, moist skin, no jaundice, no visible gross skin lesions, good skin turgor

Physical Examination Normocephalic head, no visible scalp lesions, patent anterior fontanel Pink palpebral conjunctivae, anicteric sclerae, pupils 2- 3 mm ERTL No tragal tenderness, intact tympanic membrane No nasoaural discharge, nasal septum midline, turbinates not congested Moist buccal mucosa, nonhyperemic posterior pharyngeal walls, tonsils not enlarged,

Physical Examination Supple neck, no palpable cervical lymphadenopathy, thyroid gland not enlarged Symmetrical chest expansion, (+) subcostal retractions, equal tactile and vocal fremiti, (+) crackles over both lung field with occasional wheezes at left lung field Adynamic precordium, apex beat at 4 th LICS MCL, no heaves/lifts, no thrills, normal rhythm, S1 louder than S2 at the apex, S2 louder than S1 at the base, (+) Grade II continuous murmur

Physical Examination Globular abdomen, normoactive bowel sounds, soft, no tenderness, no palpable masses, Traube’s space not obliterated Genitalia: grossly male with both descended testes Pulses are full and equal, no edema, no cyanosis

Neurologic Examination Awake, alert Cranial nerves: CNI not assessed, pupils 2-3mm equally reactive to light, (+) direct and consensual light reflex, (+) ROR, EOM full and equal, no gross facial asymmetry, gross hearing intact (able to localize sound), CN IX, X, XI, XII not assessed No spasticity, rigidy, flaccidity, no limitation in movement No sensory deficits DTR +2 No nuchal rigidity, Brudzinski’s and Kernig’s (+) Moro, grasp, plantar, sucking reflex

Salient Features 3 month old male History of colds, non-productive cough PE: tachypneic, (+) subcostal retractions, (+) crackles over both lung field with occasional wheezes at left lung field

Approach to Diagnosis Symptom, sign or laboratory finding pointing to an organ or part of an organ system

3 month old male History of colds, non-productive cough, difficulty of breathing PE: tachypneic, (+) subcostal retractions, (+) crackles over both lung field with occasional wheezes at left lung field Pulmonary Pathology Pulmonary Congestion Primary Complex Pneumonia Approach to the Diagnosis

Differential Diagnosis Difficulty of breathing 3 month old Pulmonary Congestion Primary Complex AsthmaPneumonia (-) Congestive Heart Failure No known TB exposure 10 days duration of cough (-) Fever (-) Palpable Lymphadenopathy No change in weight Dyspnea Cough (+) Wheezing Long expiratory phase? FHX of Asthma Salbutamol challenge Dyspnea Colds Cough Wheezes and crackles Previous Pneumonia

Differential Diagnosis Difficulty of breathing 3 month old Pulmonary Congestion Primary Complex AsthmaPneumonia (-) Congestive Heart Failure No known TB exposure 10 days duration of cough (-) Fever (-) Palpable Lymphadenopathy No change in weight Dyspnea Cough (+) Wheezing Long expiratory phase? FHX of Asthma Salbutamol challenge Dyspnea Colds Cough Wheezes and crackles Previous Pneumonia

Complete Blood Count BacterialViral WBC 15,000 – 40,000WBC < 20,000 GranulocytesLymphocytes Chest Xray (PA Lat) Gold standard for the diagnosis of pneumonia Indicates complications PCAP such as a pleural effusion or empyema

Admitting Diagnosis Pneumonia

COURSE IN THE WARDS

ADMITTING ORDERS NPO, Hgt every 8 hours Vital signs every hour IVF D5 IMB 500cc to run at ml/hr (100%) Input & Output recorded every shift Requested: CBC with platelets CXR Meds: Ampicillin 150mg/ SIVP over 30 Q6 hours (184 mkd) Gentamicin 13 mg/ SIVP over 30 mins Qday(348 mkd) Salbutamol nebulization 1 neb every 6 hours

In our patient...

2nd HD Ampicillin dose was increased to 160 mg/ SIVP over 30 mins, Q6 Hgt monitoring was discontinued Feeding was resumed

Nebulization was discontinued 3rd HD

6 th HD Decreased monitoring to Q4 IVF consumed

7 th HD Last dose of antibiotics given Discharged stable and improved

PPS Clinical Practice Guideline for PCAP 2004

Discussion Inflammation of parenchyma of the lungs Etiologic agent vary with the age and immune status of the child, as well as with some environmental conditions

Signs and Symptoms Symptoms of pneumonia vary, depending on the age of the child and the cause of the pneumonia. Common symptoms include: – fever – chills – cough – tachypnea – breathing with grunting or wheezing sounds – labored breathing leading to retractions – vomiting – chest pain – abdominal pain – decreased activity – loss of appetite (in older kids) or poor feeding (in infants) – in extreme cases, cyanosis

Pathophysiology results from inflammation of the alveolar space and may compromise air exchange Most commonly, this inflammation is the result of invasion by bacteria, viruses, or fungi, but it can occur as a result of chemical injury or may follow direct lung injury (eg, near drowning).

Four stages of lobar pneumonia have been described. The first stage, occurring within 24 hours of infection the lung is characterized microscopically by vascular congestion and alveolar edema Many bacteria and few neutrophils are present The stage of red hepatization (2-3 d) similarity to the consistency of liver, is characterized by the presence of many erythrocytes, neutrophils, desquamated epithelial cells, and fibrin within the alveoli

In the stage of gray hepatization (2-3 d) the lung is gray-brown to yellow because of fibrinopurulent exudate, disintegration of red cells, and hemosiderin The final stage of resolution is characterized by resorption and restoration of the pulmonary architecture Fibrinous inflammation may extend into the pleural space, causing a rub heard by auscultation, and it may lead to resolution or to organization and pleural adhesions.

Bronchopneumonia, a patchy consolidation involving one or more lobes, usually involves the dependent lung zones The neutrophilic exudate is centered in bronchi and bronchioles, with centrifugal spread to the adjacent alveoli * Bacterial superinfection of viral pneumonia : mixed pattern of interstitial and alveolar airspace inflammation

In interstitial pneumonia, patchy or diffuse inflammation involving the interstitium is characterized by infiltration of lymphocytes and macrophages The alveoli do not contain a significant exudate, but protein-rich hyaline membranes similar to those found in adult respiratory distress syndrome (ARDS) may line the alveolar spaces

Miliary pneumonia is a term applied to multiple, discrete lesions resulting from the spread of the pathogen to the lungs via the bloodstream. miliary tuberculosis, histoplasmosis, and coccidioidomycosis may manifest as granulomas with caseous necrosis to foci of necrosis Factors that bypass or inactivate local defenses (eg, tracheostomy tubes, immotile cilia syndrome) predispose the child to pneumonia The result is loss of surfactant activity with local collapse and consolidation.

Pathogens implicated in pneumonia vary with the age of the child, the underlying patient-specific risk factors, immunization status, and seasonality.

Newborns and infants via the maternal genital tract group B streptococci, Escherichia coli and other fecal coliforms, and C trachomatis. Group B streptococci most often is transmitted to the fetus in utero, usually as a result of colonization of the mother's vagina and cervix by the organism. However, most pneumonia in this age group is community acquired and involves Streptococcus pneumoniae, Staphylococcus aureus, and non- typeable Haemophilus influenzae.

Young children Viruses are a common cause of pneumonia among toddlers and preschoolers Streptococcus pneumoniae is by far the most common bacterial cause of pneumonia Children in this age group are also at risk for infection by M pneumoniae

Older children and adolescents M pneumoniae is a frequent cause of pneumonia among older children and adolescents Older adolescents may have lost their immunity to pertussis and may become infected by this organism Bacterial pneumonia in this age group most often is caused by Streptococcus pneumoniae.

Efficacy of an 11-Valent Pneumococcal Conjugate Vaccine against Radiologically Confirmed Pneumonia Among Children Less Than 2 Years of Age in the Philippines A Randomized, Double-Blind, Placebo- Controlled Trial Lucero et al The Pediatric Infectious Disease Journal Volume 28 Number 6, June 2009 Lippincott Williams and Wilkins

Pneumococcus Leading cause of childhood pneumonia worldwide Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the US and Africa No information is available from Asia on the impact of PCV on childhood pneumonia

Study Setting 6 municipalities in Bohol province in central Philippines 3 seasons: hot, rainy, cold No HIV and no malaria Infant mortality rate in Bohol: 28/1000 live births Major cause of death: pneumonia and diarrhea Study monitored by RITM and KTL

Study Design Randomized, placebo-controlled, double blind trial Collaboration with government and private health services in Bohol 3 doses of 11PCV or a saline placebo given at 4 weeks interval to determine Vaccine Efficiency

Participants Informed consent of the mother Inclusion criteria Children age <6 weeks to 6 months The family was expected to remain in the study area for 2 years or until the end of December 2004 Infant was healthy Exclusion criteria First dose DTwP Rectal temperature of 38°C Neurologic disease History of hospitalization or treatment for immune suppression Enrolment in another clinical trial

Vaccine 11 PCV 1 μg S. pneumoniae capsular polysaccharide conjugated to tetanus toxoid for types 1, 4, 5, 7F, 9V, 19F, and 23F 3μg of polysaccharide of types 3, 14, and 18C conjugated to dipththeria toxoid 10μg pf polysaccharide of type 6B conjugated to diptheria toxoid Manufactured by Sanofi pasteur Placebo Saline Vaccines were given intramuscularly in the anterolateral aspect of right thigh Routine vaccines given in left thigh

Definition of terms Community acquired pneumonia Pneumonia with onset either in the community or in hospital but less than 72 hours after admission IPD Bacteremia or culture proven meningitis Trial end point: Radiologically defined CAP using WHO vaccine trialists’ standard guidelines Presence of a dense opacity that could be a fluffy consolidation of a portion of a lobe, a whole lobe or the entire lung, often containing air bronchograms and sometimes associated with pleural effusion in the lateral pleural space Associated with a pulmonary infiltrate or an effusion large enough to obscure such an opacity

Secondary end points Hospitalized or not hospitalized Culture proven invasive disease with a vaccine type- specific pneumococcus Serious adverse events

Clinical Pneumonia (WHO Severity Grade) History of cough and/or difficulty of breathing Increased respiratory rate according to age Lower chest wall indrawing (severe) Cyanosis and/or inability to drink (very severe)

Surveillance for Clinical Episodes Blood culture Chest x-ray CSF culture when indicated Antibiotic treatment

Results July 2000-December 18, ,194 enrolled children 98.7% subjects received 3 doses of study vaccine Median age was 1.8, 2.9, and 3.9 months for vaccination

Discussion Prevention of 22.9% of radiologically defined pneumonia among children 2 years of age Age stratified analysis of Vaccine Efficacy: <12 months = 34.0% months = 2.7% Vaccine had no effect against clinical pneumonia

Conclusions 11 PCV show similar efficacy as the available 7PCV in other epidemiological and geographic settings Use of WHO-PEP as feasible end point in clinical trials and good proxy for measuring pneumococcal pneumonia 1/5 of radiologically confirmed pneumonia is caused by pneumococcus in a low income, low mortality developing country such as the Philippines, and thus preventable by PCV Inclusion in national program on immunization depends on specific disease burden measurement and cost- effectiveness calculation

Thank you!!!