The role of Pulmonary function Testing In Interstitial lung disease in infants. [ ipft in child ]
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1 The role of Pulmonary function Testing In Interstitial lung disease in infants [ ipft in child ]
2 Introduction Managing infants with diffuse lung disease (DLD) suspected to have interstitial lung disease (child) can be a challenging task. Diagnostic workup may include a vast arsenal of tests. However, it is not always clear: What to use When to use Follow-up during management (after diagnosis has been made) is usually restricted to clinical judgment and basic measurements.
3 Introduction Pulmonary function testing for ILD adults patients is an essential tool and rarely is avoided. Studies in adults have shown its potential clinical applications: aiding in diagnosis establishing disease severity predicting prognosis monitoring response to therapy and disease progression There are paucity of data regarding the use of infant pulmonary function testing (ipft) in child. In the last years, ipft have gained increased acceptance for clinical purposes.
4 Evaluation of various lung functions in Infants (major) Adult type infant lung function testing Lung volumes, Flows, Resistance, Compliance Airway occlusion techniques Resistance, Compliance Multiple-breath helium dilution Lung volumes (FRC) Multiple-breath inert gas washout Inhomogeneity of ventilation (LCI), FRC Forced oscillation technique and impulse oscillometry Impedance, Resistance
5 Adult type infant lung function testing Various lung volumes TLC, VC, FRC, RV, V T, etc Forced expiration flows Tidal breathing rapid thoracoabdominal compression technique forced expiration techqneuiqe V maxfrc Raised volume rapid thoracoabdominal compression technique FEF 0.5, FEF 75% and FEF 85% Resistance AW Compliance AW
6 ipft in child evaluation ipft can be helpful in three junctures Helping to decide at which point the evaluation of an infant with DLD be expanded. Making a definite diagnosis Follow-up after diagnosis Response to treatment
7 child evaluation
8 child evaluation- The ATS clinical practice guideline All neonates and infants (< 2 yr of age) with diffuse lung disease (DLD) should have common diseases that can cause DLD excluded as the primary diagnosis. CF, Immundeficiency, BPD, Infection, CHD, PCD, Rec. aspiration child syndrome common diseases that can cause DLD have been eliminated & three of the following four criteria are present: Respiratory symptoms respiratory signs Hypoxemia Diffuse abnormalities on a chest radiograph or CT scan We recommend diagnostic testing to determine the exact child diagnosis (strong recommendation).
9 child evaluation When should the evaluation of an infant with DLD be expanded? The ATS clinical practice guideline: The urgency, the choice of diagnostic tests, whether to perform genetic testing and/or to proceed to lung biopsy depend upon numerous factors. These include the clinical context and disease severity, acuity, and duration. However.. in a significant portion of the cases even after the integration of the above factors, there is no agreed specific timeframe as to when the "second" line of diagnostic tools should be implemented!
10 child evaluation- The ATS clinical practice guideline in infants presenting at over 1 month of age
11 Kuo CS, Young LR. Interstitial lung disease in children. Curr Opin Pediatr. Jun 2014
12 child evaluation ipft Can demonstrate the physiologic alteration Does not use radiation Can be repeated more comfortably if needed Can not establish a definitive diagnosis Requires some degree of sedation.
13 child evaluation When should the evaluation of an infant with DLD be expanded? Can ipft be helpful?
14 child evaluation 1. At what juncture should the evaluation of an infant with DLD be expanded? Can ipft be helpful? ipft Reduced lung volumes compliance DLCO (if available) Restrictive alteration D.D. (examples) Surfactant dysfunction mutations PIG Proceed with evaluation? Normal lung volumes airway flows RS compliance Watchful waiting? air trapping airflow obstruction Obstructive alteration D.D. (main) BO / BPD / NEHI / Long lasting bronchiolitis / other infections Any known specific treatment? Waiting?
15 2. Obtaining a definitive diagnosis child evaluation Can ipft be helpful? ipft Reduced lung volumes compliance DLCO (if available) Restrictive alteration D.D. (examples) Surfactant dysfunction mutations PIG Proceed with evaluation?
16 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) Length (cm) Oxygen saturation (%RA) 3.9 (<3 percentile) 57 (<3 percentile) 3.8 (<3 percentile) 54 (<3 percentile) 88 91
17 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) Length (cm) Oxygen saturation (%RA) 3.9 (<3 percentile) 57 (<3 percentile) 3.8 (<3 percentile) 54 (<3 percentile) 88 91
18 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) 3.9 (<3 percentile) 3.8 (<3 percentile) Length (cm) 57 (<3 percentile) 54 (<3 percentile) Oxygen saturation (%RA) Respiratory Rate (breaths/min) V T (ml/kg) (normal range ml/kg) Ve/kg (ml/min/kg) (normal <300)
19 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) 3.9 (<3 percentile) 3.8 (<3 percentile) Length (cm) 57 (<3 percentile) 54 (<3 percentile) Oxygen saturation (%RA) Respiratory Rate (breaths/min) V T (ml/kg) (normal range ml/kg) Ve/kg (ml/min/kg) (normal <300) Crs (ml/cmh2o) Crs/kg (normal >1)
20 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) 3.9 (<3 percentile) 3.8 (<3 percentile) Length (cm) 57 (<3 percentile) 54 (<3 percentile) Oxygen saturation (%RA) Respiratory Rate (breaths/min) V T (ml/kg) (normal range ml/kg) Ve/kg (ml/min/kg) (normal <300) Crs (ml/cmh2o) Crs/kg (normal >1) VC ml (% pred) 92 (52%) 28 (69%) TLC ml (% pred) 196 (74%) 211 (94%) FRC ml (% pred) 128 (110%) 138 (125%) RV ml (% pred) 104 (99%) 108 (109%)
21 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) 3.9 (<3 percentile) 3.8 (<3 percentile) Length (cm) 57 (<3 percentile) 54 (<3 percentile) Oxygen saturation (%RA) Respiratory Rate (breaths/min) V T (ml/kg) (normal range ml/kg) Ve/kg (ml/min/kg) (normal <300) Crs (ml/cmh2o) Crs/kg (normal >1) VC ml (% pred) 92 (52%) 28 (69%) TLC ml (% pred) 196 (74%) 211 (94%) FRC ml (% pred) 128 (110%) 138 (125%) RV ml (% pred) 104 (99%) 108 (109%) 416 (263%) 343 (245%) FEF 75 ml/sec (% pred) 410 (207%) 579 (334%) FEF 85 ml/sec (% pred) 295 (258%) 477 (476%)
22 child evaluation ipft results of 2 infants with DLD Patient 1 Patient 2 Age (months) Weight (kg) 3.9 (<3 percentile) 3.8 (<3 percentile) Length (cm) 57 (<3 percentile) 54 (<3 percentile) Oxygen saturation (%RA) Respiratory Rate (breaths/min) V T (ml/kg) (normal range ml/kg) Ve/kg (ml/min/kg) (normal <300) Crs (ml/cmh2o) Crs/kg (normal >1) VC ml (% pred) 92 (52%) 28 (69%) TLC ml (% pred) 196 (74%) 211 (94%) FRC ml (% pred) 128 (110%) 138 (125%) RV ml (% pred) 104 (99%) 108 (109%) 416 (263%) 343 (245%) FEF 75 ml/sec (% pred) 410 (207%) 579 (334%) FEF 85 ml/sec (% pred) 295 (258%) 477 (476%)
23 ipft shows restrictive pattern child evaluation Chest x-ray, HRCT scans of the chest and Lung biopsy of Patient 1 & Patient 2 HRCT Areas of ground-glass opacities Diffuse interstitial thickening, Areas of hyperinflation Lung Biopsy Interstitial process with thickening and hypercellularity of alveolar sepata due to a proliferation type II pneumocytes Focal accumulation of macrophages in the alveolar spaces
24 ipft shows restrictive pattern child evaluation Chest x-ray, HRCT scans of the chest and Lung biopsy of Patient 1 & Patient 2 Chronic pneumonitis of Infancy (CPI) Treatment with P.O. steroids & hydroxychloroquine was started
25 child evaluation restrictive pattern in ipft CPI pathology on Biopsy Genetic testing for surfactant proteins
26 child evaluation Clinical DLD (Appropriate CT appearance) surfactant and related gene mutation Definitive diagnosis of Surfactant dysfunction related disorder?
27 child evaluation Clinical DLD (Appropriate CT appearance) surfactant and related gene mutation ipft demonstrating restrictive alteration Definitive diagnosis of Surfactant dysfunction related disorders
28 child evaluation ipft for obtaining a definitive diagnosis Z-score FVC= FEF75%= DLCO/VA= Ehsan, pediatric pulmonology 2014
29 child evaluation ipft for obtaining a definitive diagnosis Second example
30 child evaluation Clinical DLD
31 child evaluation Clinical DLD Definitive diagnosis of NEHI?
32 child evaluation Clinical DLD ipft demonstrating classic alteration Definitive diagnosis of NEHI
33 child evaluation Clinical DLD ATS guideline for child ipft demonstrating classic alteration Definitive diagnosis of NEHI Biopsy
34 Young, Chest 2011 ipft in NEHI
35 Young, Chest 2011 ipft in NEHI
36 Young, Chest 2011 ipft in NEHI
37 Disease control subjects (light gray), NEHI syndrome subjects (dark gray), NEHI subjects (white) Kerby, Pediatric pulmonology
38 ipft in NEHI results from our Lab VmaxFRC פ.ש פ.ח ד.ב ד.א ק.א pred) VmaxFRC (% נורמה FRC FVC FRC (% pred) פ.ש פ.ח ד.ב ד.א ק.א נורמה פ.ש פ.ח ד.ב ד.א ק.א נורמה FVC (% pred) It seems that the air tapping in NEHI is more prominent than BO compared to the expiratory airway obstruction. There are some cases of NEHI with air trapping without airway obstruction
39 ipft in newborn diagnosed with C.F. by screening Nguyen TT et al, Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants, Thorax 2014
40 Follow-up after diagnosis Response to treatment child evaluation For this purpose it seems that beyond clinical judgment and bedside tools such as SPO 2, no other sufficient tool exists. Repeated HRCT? Repeated lung biopsies? Can ipft be helpful?
41 ipft in the follow-up of child Two patients with CPI restrictive pattern in ipft CPI pathology on Biopsy Genetic testing for surfactant proteins Treatment with P.O. steroids & hydroxychloroquine was started
42 ipft in the follow-up of child Patient 1 Patient 2 Beginning of treatment Beginning of pulse steroid Discontinuation of treatment Beginning of treatment Beginning of pulse steroid Discontinuation of treatment
43 ipft in the follow-up of child -2 Three infants with histologically confirmed chronic interstitial pneumonitis
44 Three infants with histologically confirmed chronic interstitial pneumonitis
45 ipft in the follow-up of child NEHI patients Correlation between ipft (FRC and FEV 0.5 ) and Later SPO 2 Spirometry indices (FEV 1, FEF 25%-75% and FVC) measured 4 to 5 years later. Kerby GS et al Abnormal infant pulmonary function in young children with neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol. 2013
46 Summary Managing infants with DLD or child can be a challenging task, and it seems that more tools are needed for help with decisions making. PFT s are essential tool in management of adult ILD patients, however there are paucity of data regarding the use of ipft in child. ipft can help in deciding when the evaluation of DLD infants should be expanded. ipft can establish the diagnosis of specific etiology and eliminate the need for biopsy. NEHI - appropriate clinical course + HRCT + ipft Surfactant protein Def.: appropriate clinical course + HRCT + Genetic testing + ipft ipft may be the only tool for follow-up during management of child confirmed infants ( including at research)
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