Research Related To Spirometry In Children

Disclaimer: This information is intended for educational purposes and should not be considered medical advice. Clinical decisions must always be made by a qualified healthcare professional based on individual patient circumstances, current medical evidence, and professional judgment. This content is not a substitute for professional medical advice, diagnosis, or treatment.

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Overview

Definition

Spirometry is a fundamental physiological test measuring how much air a person can inhale and exhale, and how quickly. In children, it is a non-invasive, effort-dependent test used to assess lung function, identify obstructive or restrictive ventilatory patterns, monitor disease progression, and evaluate response to therapy. Research in pediatric spirometry focuses on optimizing its technique, interpretation, and clinical utility across various age groups and respiratory conditions.

Epidemiology

Research indicates that spirometry is increasingly utilized in pediatric respiratory care, though its accessibility and consistent application vary globally. - Prevalence of Abnormal Lung Function: Studies frequently use spirometry to determine the prevalence of obstructive or restrictive lung patterns in conditions like asthma (up to 30-50% in symptomatic children), cystic fibrosis (nearly all affected), or bronchopulmonary dysplasia (variable, but often significant impairment). - Utilization Rates: Research highlights disparities in spirometry utilization, with lower rates in primary care settings compared to specialist clinics, and challenges in specific populations (e.g., very young children, children with neurodevelopmental disorders). Efforts are ongoing to improve access and training. - Normal Reference Values: A critical area of research involves establishing and validating appropriate race/ethnic-specific and age-specific reference equations, given significant differences in lung volumes and flows based on anthropometric factors and population characteristics. The Global Lung Function Initiative (GLI) 2012 equations are widely adopted and continuously researched for their applicability across diverse pediatric populations.

Classification

Research often classifies spirometry findings in children based on ventilatory patterns and severity, adhering to international guidelines (e.g., ATS/ERS): - Normal Spirometry: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), FEV1/FVC ratio, and Forced Expiratory Flow at 25-75% of FVC (FEF25-75%) are within normal limits (typically > Lower Limit of Normal [LLN], corresponding to a z-score > -1.64 for GLI). - Obstructive Pattern: Characterized primarily by a reduced FEV1/FVC ratio (below LLN), often with reduced FEV1 and FEF25-75%. Severity is typically graded by FEV1 % predicted (mild: ≥70%, moderate: 60-69%, severe: 50-59%, very severe: <50%). - Restrictive Pattern: Characterized by a reduced FVC (below LLN) with a preserved or elevated FEV1/FVC ratio (above LLN). Requires further investigation with lung volumes (Total Lung Capacity - TLC) for confirmation. - Mixed Pattern: Reduced FEV1/FVC ratio and reduced FVC. - Bronchodilator Responsiveness (BDR): Significant improvement in FEV1 or FVC after bronchodilator administration (typically ≥12% and ≥200 mL increase in FEV1 or FVC from baseline) is indicative of airway reversibility, particularly relevant in asthma diagnosis and management. Research continues to refine BDR criteria and its prognostic value in children.

Pathophysiology

Mechanism

Research uses spirometry to understand the underlying pathophysiology of various pediatric respiratory conditions. Spirometry does not have a "pathophysiology" itself, but rather reflects the mechanical properties of the lungs and airways. - Airway Obstruction: Reduced FEV1/FVC ratio reflects increased airway resistance, as seen in asthma (bronchoconstriction, inflammation, remodeling), cystic fibrosis (mucus plugging, inflammation, bronchiectasis), and bronchiolitis obliterans. Research investigates how these underlying cellular and molecular mechanisms manifest as spirometric changes. - Lung Parenchymal Disease: Reduced FVC with preserved FEV1/FVC ratio indicates decreased lung volume or compliance, common in interstitial lung diseases, neuromuscular disorders affecting respiratory muscles, or severe scoliosis. Spirometry helps quantify the functional impact of these structural changes. - Small Airway Dysfunction: Research suggests that FEF25-75% and other forced expiratory flow parameters may be early indicators of small airway dysfunction, particularly in conditions like asthma, prematurity-related lung disease, or post-viral bronchiolitis, even when FEV1 and FVC are relatively preserved. This area is subject to ongoing research regarding its sensitivity and specificity.

Risk Factors

Research identifies several factors that can influence the acquisition and interpretation of spirometry results in children: - Age: Younger age is a significant risk factor for poor effort and non-reproducible results. Preschool spirometry (ages 3-6) requires specialized techniques and highly trained staff. - Cooperation and Effort: Spirometry is effort-dependent. Lack of understanding, fear, or neurological immaturity can lead to sub-optimal maneuvers. - Anthropometric Factors: Age, height, sex, and ethnicity are critical for accurate interpretation against reference values. Mismatched reference equations lead to misclassification. - Underlying Medical Conditions: Conditions affecting neurocognitive function (e.g., cerebral palsy, autism) or physical ability (e.g., muscular dystrophy, severe scoliosis) can impair test performance. - Equipment and Technician Factors: Incorrect calibration, poorly maintained equipment, or inadequately trained technicians can lead to erroneous results.

Protective Factors

Research aims to identify factors that improve the quality and utility of pediatric spirometry: - Experienced and Patient Technicians: Trained staff skilled in motivating and coaching children are crucial for obtaining acceptable and reproducible maneuvers. - Child-Friendly Environment and Coaching: Using age-appropriate language, visual aids, and positive reinforcement significantly improves cooperation. - Appropriate Equipment: Spirometers calibrated and validated for pediatric use, with low resistance and suitable mouthpieces. - Standardized Protocols: Adherence to ATS/ERS guidelines for maneuver performance, acceptability, and reproducibility criteria ensures reliable data. - GLI 2012 Reference Equations: Use of globally validated, all-age, multi-ethnic reference equations minimizes misclassification based on inappropriate reference data.

Clinical Presentation

Signs and Symptoms

Spirometry is performed in children presenting with various respiratory signs and symptoms that suggest underlying lung disease: - Cardinal Features: Persistent cough (especially nocturnal or exercise-induced), recurrent wheezing, shortness of breath, exercise intolerance. - Early Signs: Subtle cough, increased respiratory rate, recurrent respiratory infections, prolonged recovery from common colds. - Advanced Signs: Cyanosis, clubbing, severe dyspnea at rest, failure to thrive. Spirometry in these cases helps quantify the severity of impairment. - Atypical Presentations: Chest pain, recurrent pneumonia, stridor, or sleep-disordered breathing may prompt spirometry to evaluate underlying lung mechanics.

Physical Examination

Physical examination findings guide the clinician to consider spirometry and help interpret the results in context. Spirometry itself does not have physical exam findings. - Inspection: Signs of respiratory distress (tachypnea, retractions, nasal flaring), digital clubbing, barrel chest (e.g., in severe asthma, CF), spinal deformities (e.g., scoliosis). - Palpation: Symmetrical chest expansion, tactile fremitus. - Special Tests: Not directly related to spirometry. However, the presence of specific findings (e.g., hypertrophic accessory muscles of respiration) reinforces the need for comprehensive lung function assessment.

Diagnostic Approach

History Taking

When interpreting spirometry in children, a thorough history is paramount, as emphasized in research on diagnostic accuracy. - Key Questions: - Demographics: Age (crucial for effort, cooperation), height (essential for % predicted values), sex, ethnicity. - Symptoms: Type, onset, duration, triggers (e.g., allergens, exercise, cold air), nocturnal vs. daytime. - Medical History: Prematurity, history of bronchiolitis, recurrent infections, allergies, eczema, food allergies, gastroesophageal reflux, heart disease, neuromuscular conditions. - Medications: Current respiratory medications (e.g., inhaled corticosteroids, bronchodilators), recent use of short-acting bronchodilators before testing. - Environmental Exposures: Tobacco smoke, indoor/outdoor allergens, air pollution. - Family History: Asthma, allergies, cystic fibrosis, other lung diseases. - Previous Spirometry: Trends over time are crucial. - Red Flags: - Lack of Symptom-Spirometry Correlation: Significant symptoms with normal spirometry, or severe spirometric abnormality with minimal symptoms, warrants careful review for technical issues, alternative diagnoses, or poor effort. - Sudden Significant Decline: An unexpected, rapid drop in lung function (e.g., FEV1 >10-15% over a short period) requires urgent investigation for acute exacerbation, new pathology, or poor technique. - Inability to Perform Acceptable Maneuvers: In an older child, this could indicate severe airflow limitation or neuromuscular weakness needing further evaluation.

Laboratory Tests

Research often examines the correlation between spirometry and other diagnostic markers, though spirometry rarely requires preceding lab tests. - First-Line: Not applicable for spirometry itself. Spirometry is often a first-line functional test. - Confirmatory: Spirometry findings (e.g., obstructive pattern) might prompt confirmatory tests like sweat chloride test for cystic fibrosis, alpha-1 antitrypsin levels, or immunology work-up. - Monitoring: Spirometry is a key monitoring tool. Blood tests (e.g., inflammatory markers, IgE levels) might be used in conjunction to monitor disease activity in certain conditions (e.g., eosinophilic asthma).

Imaging

Research investigates the relationship between spirometric abnormalities and structural changes on imaging. - Recommended: - Chest X-ray: Often performed prior to spirometry in undiagnosed lung disease to rule out gross structural abnormalities, pneumonia, or foreign body. - High-Resolution Computed Tomography (HRCT): Recommended in cases of persistent, unexplained spirometric abnormalities (e.g., restrictive pattern, severe fixed obstruction) to identify bronchiectasis, interstitial lung disease, or other structural abnormalities not evident on plain film. Research links specific spirometric patterns to HRCT findings in CF, BPD, and primary ciliary dyskinesia. - Advanced: - Ventilation-Perfusion (V/Q) Scan: Rarely used in conjunction with spirometry, but can be useful in specific research settings (e.g., chronic thromboembolic disease). - Magnetic Resonance Imaging (MRI): Emerging research explores its role in assessing lung structure and function, sometimes complementing spirometry, particularly in situations where radiation exposure is a concern.

Management

Acute Management

Spirometry's role in acute management is primarily diagnostic and for guiding immediate treatment. Research validates its utility. - Immediate: In an acute asthma exacerbation, bedside spirometry (if feasible and safe) can assess severity (e.g., FEV1 <50% predicted indicates severe obstruction) and guide initial bronchodilator therapy. Research supports its use in the emergency department for objective assessment. - Stabilization: Following initial bronchodilator treatment, repeat spirometry can help assess response and guide escalation or de-escalation of therapy. - Emergency: In a severe asthma attack, spirometry is often not feasible or safe due to patient distress. Clinical assessment takes precedence. However, in less severe cases, it can help differentiate conditions.

Chronic Management

Spirometry is an indispensable tool in the long-term management of chronic pediatric respiratory diseases. Research consistently demonstrates its value. - Pharmacological: - Asthma: Regular spirometry (e.g., every 3-6 months in uncontrolled asthma, annually in controlled) monitors lung function trends, identifies fixed airflow obstruction, and assesses bronchodilator response. Research shows that spirometry-guided adjustments of inhaled corticosteroids can optimize control. - Cystic Fibrosis (CF): Annual or more frequent spirometry (e.g., FEV1, FVC, FEF25-75%) is crucial for monitoring disease progression, detecting early decline (e.g., >5% drop in FEV1), and assessing response to disease-modifying therapies (e.g., CFTR modulators). Research on prognostic value of FEV1 decline is robust. - Bronchopulmonary Dysplasia (BPD): Spirometry is used to track lung function development and identify chronic airflow limitation or restrictive patterns in children born prematurely. - Non-pharmacological: - Pulmonary Rehabilitation: Spirometry tracks improvements in lung function and exercise capacity in children undergoing pulmonary rehab. - Nutritional Support: In conditions like CF, spirometry helps monitor the impact of nutritional status on lung function. - Monitoring: - Trend Analysis: The most critical aspect is monitoring changes in lung function over time, using individual patient's best values as baseline. A decline of FEV1 by >10% predicted or >100-200 mL in an older child is clinically significant and warrants investigation. - Quality Control: Regular quality control checks of spirometry equipment and technician training are essential for reliable long-term monitoring, as emphasized by research on data integrity.

Treatment Algorithms

Research informs how spirometry results integrate into pediatric treatment algorithms. - First-Line: For conditions like asthma, spirometry helps confirm diagnosis and classify severity, guiding initial pharmacological therapy (e.g., step-up/step-down approach based on FEV1 % predicted and bronchodilator response). - Second-Line: If lung function deteriorates despite first-line therapy, spirometry helps assess the degree of decline and prompts consideration of alternative or add-on therapies. - Refractory Cases: In children with persistent lung function decline despite maximal therapy, spirometry helps characterize the severity of impairment and may prompt referral for specialized evaluation (e.g., lung transplant in CF) or novel therapies investigated in clinical trials. Research continually seeks to identify spirometric markers that predict treatment failure or response.

Complications

Spirometry itself is generally safe with minimal direct complications (e.g., transient lightheadedness, cough). The "complications" relevant to research are more about the consequences of misinterpretation or technical errors. - Common: - Poor Effort/Non-Reproducible Results: This is the most common "complication" in pediatric spirometry, leading to unreliable data. Research focuses on improving coaching techniques and developing objective quality indices. - Misinterpretation: Inexperienced clinicians may misinterpret results (e.g., classifying a child as obstructive based on age-inappropriate reference ranges or inadequate effort), leading to incorrect diagnosis or unnecessary treatment. - Overdiagnosis/Underdiagnosis: Incorrect application or interpretation can lead to inappropriate diagnoses (e.g., diagnosing asthma in a child with viral-induced wheeze) or missing true lung disease. - Serious: - Misdiagnosis Leading to Inappropriate Therapy: For example, prescribing long-term inhaled corticosteroids for a child with a non-asthmatic cough based on technically flawed spirometry, or missing a progressive restrictive lung disease. - Delayed Diagnosis of Progressive Disease: Failing to detect early lung function decline due to poor quality spirometry or misinterpretation can delay critical interventions for conditions like CF or interstitial lung disease, impacting long-term prognosis. - Long-term: - Patient Burden and Cost: Repeated spirometry, especially if quality is consistently poor, can be frustrating for children and families and lead to unnecessary healthcare costs. - Psychological Impact: Labeling a child with a chronic lung disease based on incorrect spirometry can have psychological consequences.

Prognosis

Research increasingly investigates the prognostic value of spirometry in pediatric respiratory conditions. - Factors: - Baseline Lung Function (FEV1%): Lower baseline FEV1% predicted is a consistent predictor of worse prognosis in CF and severe asthma. - Rate of Decline: Rapid decline in FEV1 (e.g., >2% per year in CF after age 6) is a strong prognostic indicator for increased morbidity and mortality. Research actively seeks to identify predictors of rapid decline. - Bronchodilator Responsiveness: The presence and magnitude of BDR can be prognostic in asthma, though its precise role in long-term outcomes is an active area of research. Fixed airflow obstruction (lack of BDR) suggests more severe disease and worse prognosis. - Small Airway Indices (FEF25-75%): Research explores FEF25-75% as an early prognostic marker in various conditions, although its variability limits its standalone use. - Survival: In conditions like CF, FEV1 has been historically a key determinant of survival. Research into new therapies and early intervention aims to improve survival curves linked to FEV1 trajectories. - Quality of Life: Spirometric parameters correlate with health-related quality of life (HRQoL) in children with chronic lung diseases. Research uses spirometry as an objective outcome measure in trials evaluating interventions aimed at improving QoL.

Prevention

Spirometry plays a significant role in secondary and tertiary prevention in pediatric respiratory health. - Primary: Not directly applicable to preventing disease itself. However, research into normal lung development uses spirometry to understand factors influencing optimal lung growth from infancy, which might inform primary prevention strategies for optimal respiratory health (e.g., avoiding prenatal smoke exposure). - Secondary: - Early Detection: Spirometry facilitates early detection of lung function abnormalities in at-risk populations (e.g., premature infants, children with recurrent wheezing, siblings of CF patients), allowing for early intervention before irreversible changes occur. - Screening: Research is ongoing regarding the utility of spirometry as a screening tool in high-risk pediatric populations (e.g., those exposed to environmental pollutants). - Tertiary: - Preventing Complications: Regular spirometry monitors the effectiveness of therapies in chronic lung diseases (e.g., asthma, CF), allowing for timely adjustment of treatment to prevent acute exacerbations, irreversible lung damage, and long-term sequelae. - Identifying Treatment Failure: Early identification of lung function decline via spirometry can prompt further investigation and prevent progression to end-stage lung disease.

Special Populations

Research continuously refines spirometry techniques and interpretation for diverse pediatric groups. - Pediatric: - Preschool Children (3-6 years): Requires specialized coaching and equipment (e.g., incentive-based programs, shorter exhalation times). Research focuses on establishing reliable methods and valid reference equations for this challenging age group. Preschool spirometry, while challenging, is increasingly recognized for its utility in diagnosing conditions like preschool asthma. - Infants and Toddlers (<3 years): Standard spirometry is generally not feasible. Techniques like tidal breathing analysis, forced oscillation technique (FOT), or raised volume rapid thoracic compression are research tools used to assess lung mechanics in this age group. - Children with Chronic Diseases: - Cystic Fibrosis (CF): Spirometry is central to CF management. Research explores the earliest detectable spirometric changes (e.g., FEF25-75%) and the utility of advanced techniques like Lung Clearance Index (LCI) for assessing small airway disease. - Bronchopulmonary Dysplasia (BPD): Children with BPD often have persistent airflow obstruction and reduced lung volumes. Spirometry tracks their lung growth and identifies those at risk for chronic respiratory symptoms. - Neuromuscular Disorders: Spirometry is vital for monitoring respiratory muscle strength (FVC is a surrogate) and guiding decisions on respiratory support. Specific protocols and reference values may be needed. - Geriatric: Not applicable to this topic. - Pregnancy: Not applicable to this topic. - Comorbidities: - Obesity: Research highlights that obesity can affect spirometry parameters (e.g., reduced FVC, FEV1 due to restrictive physiology), requiring careful interpretation and specific reference equations. - Congenital Heart Disease: Children with certain CHD (e.g., pulmonary hypertension, post-surgical effects) may have abnormal spirometry reflecting altered lung mechanics and vascular issues. - Scoliosis/Chest Wall Deformities: These conditions can cause restrictive ventilatory patterns, which spirometry can quantify.

Clinical Pearls

Diagnostic

• Quality Over Quantity: Emphasize obtaining acceptable and reproducible maneuvers over numerous technically flawed ones. ATS/ERS criteria (3 acceptable maneuvers, 2 best within 0.150L) are paramount.
• Child-Friendly Environment: Create a calm, engaging, and non-threatening atmosphere. Use positive reinforcement, praise effort, and make it a game.
• GLI 2012 First: Always use the Global Lung Function Initiative (GLI) 2012 reference equations, which provide z-scores for all ages and major ethnic groups, minimizing misclassification.
• Beyond % Predicted: While % predicted values are useful, the z-score (number of standard deviations from the mean) offers a more precise statistical measure and is preferred for interpretation, especially for identifying values below the Lower Limit of Normal (LLN, z-score -1.64).
• FEV1/FVC Ratio is Key for Obstruction: The FEV1/FVC ratio (below LLN) is the primary indicator of obstruction in children. FEV1% predicted reflects severity.
• FEF25-75% for Early Changes: While highly variable, a significantly reduced FEF25-75% can be an early indicator of small airway dysfunction, even with normal FEV1 and FVC, warranting further clinical correlation.

Treatment

• Trend, Not Single Value: Focus on the trend of lung function over time in chronic conditions. A significant decline (e.g., 10-15% FEV1 drop from personal best) is more clinically meaningful than a single abnormal value.
• Bronchodilator Reversibility Guides Therapy: Significant BDR (≥12% and ≥200 mL increase in FEV1 or FVC) is a strong indicator for bronchodilator therapy in symptomatic children.
• Fixed Obstruction Means More: Persistent obstruction despite bronchodilator therapy suggests fixed airway remodeling or other structural issues, requiring more intensive management and investigation.
• Patient Education: Educate children and parents on the importance of spirometry for monitoring their lung health and treatment effectiveness.

Pitfalls

• Incorrect Reference Equations: Using outdated or inappropriate reference equations is a common pitfall leading to misdiagnosis (e.g., using adult equations or single-ethnic equations for diverse populations).
• Poor Maneuver Quality: The most frequent pitfall. Results from suboptimal effort (e.g., glottic closure, cough, short exhalation, submaximal inspiration) are unreliable and should be rejected.
• Over-reliance on % Predicted: Blindly interpreting results solely by % predicted can be misleading; always look at the z-score and the LLN.
• Ignoring Clinical Context: Spirometry results must always be interpreted in the full clinical context of the child's symptoms, physical exam, and other diagnostic findings. A normal spirometry does not rule out all lung pathology.
• Misinterpreting FEF25-75%: While an early marker, its high variability makes it an unreliable standalone diagnostic or monitoring tool without other supporting evidence.

Recent Updates

Guidelines

• Global Lung Function Initiative (GLI) 2012 Equations: These remain the current gold standard for interpreting spirometry in children and adults across all major ethnic groups. Ongoing research validates and explores nuances of their application.
• ATS/ERS 2022 Updates for Spirometry Quality and Interpretation: While not specifically for pediatrics, these updates refine criteria for acceptable and reproducible maneuvers, which are highly relevant for pediatric practice, emphasizing the importance of excellent coaching. Future pediatric-specific guidelines are expected to incorporate these.
• European Respiratory Society (ERS) Preschool Spirometry Guidelines: These have significantly advanced the field, providing detailed guidance for testing and interpreting spirometry in children aged 3-6 years.

Evidence

• Longitudinal Studies: Increasing evidence from birth cohorts and longitudinal studies tracking lung function from early childhood into adulthood, highlighting the importance of early life events (e.g., prematurity, early-life infections, environmental exposures) on long-term lung health trajectories as measured by spirometry.
• Impact of CFTR Modulators: Recent research overwhelmingly demonstrates the significant and sustained improvement in FEV1 and other spirometric parameters in children with CF receiving CFTR modulator therapy, transforming prognosis.
• Remote Spirometry: Research is exploring the feasibility and accuracy of remote or home spirometry for monitoring chronic conditions in children, potentially increasing access and convenience, though challenges remain regarding quality control.
• Artificial Intelligence (AI) in Spirometry: Emerging research investigates AI algorithms for automated quality control, interpretation assistance, and potentially early disease detection from spirometry data, particularly relevant for reducing human error and increasing efficiency.

Controversies

• Clinical Utility of Preschool Spirometry: While guidelines exist, the routine use and cost-effectiveness of preschool spirometry in general pediatric practice remain debated, given the challenges in obtaining quality data and the need for specialized equipment/training.
• Significance of Isolated FEF25-75% Reduction: The clinical significance of an isolated reduction in FEF25-75% in the absence of other spirometric abnormalities continues to be a topic of debate and ongoing research, with some advocating for its use as a marker for small airway disease and others cautioning against over-interpretation due to high variability.
• Bronchodilator Reversibility Criteria: While ATS/ERS defines BDR, there's ongoing discussion about refining the criteria for different pediatric age groups and conditions, and its precise prognostic value in children with early asthma symptoms.

Key References

Guidelines

• Graham, B. L., et al. (2019). ERS/ATS Standards for Respiratory Function Testing: Quality Control, Standardization of Procedures, and Interpretation of Spirometry. European Respiratory Journal, 53(1), 1801907. (This is the overarching adult guideline, but principles apply to children).
• Miller, M. R., et al. (2005). Standardisation of spirometry. (ATS/ERS Statement). European Respiratory Journal, 26(2), 319-338. (Older, but foundational).
• Quanjer, P. H., et al. (2012). Multi-ethnic reference values for spirometry for the 3-95-yr age range: The Global Lung Function Initiative (GLI) 2012 equations. European Respiratory Journal, 40(6), 1324-1343. (Essential for interpretation).
• Beydon, N., et al. (2017). An official ERS/ATS statement: pulmonary function testing in preschool children. European Respiratory Journal, 50(1), 1600975. (Specific guidance for young children).

Studies

• Stick, S. M., et al. (2019). Early-life origins of lung disease. Nature Reviews Clinical Oncology, 16(10), 629-644. (Review of longitudinal studies).
• Davies, J. C., et al. (2018). Efficacy and safety of ivacaftor in patients aged 6-11 years with cystic fibrosis with a G551D mutation: a multicentre, open-label, phase 3a study. Lancet Respiratory Medicine, 6(7), 532-540. (Example of CFTR modulator research on lung function).
• Stocks, J., et al. (2009). Reference values for lung function in Caucasian children and adolescents: Primary and secondary endpoints of an international study. European Respiratory Journal, 34(6), 1388-1403. (One of the large foundational studies contributing to GLI).

Reviews

• Pinto, M., et al. (2020). Spirometry in children: new insights for old challenges. Current Opinion in Allergy and Clinical Immunology, 20(2), 173-178.
• Bush, A., & Stocks, J. (2014). Lung function in children with cystic fibrosis: from infancy to adulthood. Clinical Chest Medicine, 35(1), 1-13.
• Aurora, P., et al. (2015). Lung function in preterm infants and children: what are the consequences of preterm birth for lung function and respiratory morbidity later in life? Pediatric Research, 77(2), 187-195.