Pulmonary

47-80%
Strong

for primary ciliary dyskinesia with extended gene panels

System Profile

Yield Comparison

Clinical Dimensions

  • Recurrent pneumonias
  • Chronic wet cough
  • Unexplained respiratory distress
  • Neonatal respiratory failure
  • Cystic fibrosis
  • Primary ciliary dyskinesia
  • Surfactant protein deficiencies
  • Congenital diaphragmatic hernia with syndromic features
  • Digital clubbing
  • Nasal polyps
  • Chest wall deformities
  • Retractions
  • Chronic wet cough on exam
  • Crackles or wheezes not explained by typical asthma
  • Chronic cough
  • Daily wet cough
  • Recurrent pneumonia
  • Wheezing poorly responsive to therapy
  • Nighttime breathing issues
  • Snoring or apnea
  • Elevated sweat chloride
  • Borderline sweat test with CFTR mutation
  • Low nasal nitric oxide
  • Eosinophilia in some genetic lung diseases
  • Arterial blood gas abnormalities
  • Chest CT showing bronchiectasis
  • Mosaic perfusion
  • Situs inversus
  • Interstitial lung disease
  • Congenital airway malformations
  • Ground-glass opacities in infants
  • Ciliary biopsy showing immotile or dyskinetic cilia
  • Low nasal nitric oxide on PCD screening
  • Sweat chloride confirmatory for CF
  • PFT with unexplained obstruction/restriction
  • Chronic inhaled steroids
  • Long-term antibiotics for bronchiectasis
  • CFTR modulators
  • Home oxygen
  • Nebulized therapies
  • Severe bronchospasm or anaphylactoid response not fully explained by atopy
  • Unusual sensitivity to inhaled agents
  • Lobectomy for congenital airway malformations
  • Tracheostomy
  • Diaphragmatic hernia repairs
  • Lung biopsy for interstitial disease
  • Chest PT
  • Airway clearance therapies (vest, manual percussion)
  • CF clinic respiratory protocols
  • Home oxygen
  • CPAP/BiPAP
  • Airway clearance vests
  • Nebulizer equipment
  • Tracheostomy hardware
  • Pulmonology/CF clinic/PCD center
  • Chronic respiratory team
  • Pulmonologist recommending CFTR or PCD testing
  • Cystic fibrosis
  • Chronic lung disease in childhood
  • Bronchiectasis
  • Situs inversus
  • Recurrent pneumonias in multiple relatives
  • No secondhand smoke or environmental pollutants explaining chronic cough and bronchitis
  • Similar pulmonary history in siblings
  • Symptoms from infancy
  • Respiratory distress requiring oxygen or ventilation without clear infection
  • PPHN
  • Pneumothorax
  • Recurrent early pneumonias

Red Flag Combinations

Clinical patterns that should prompt consideration of genetic testing

Chronic wet cough + situs inversus
Recurrent pneumonia + pancreatic insufficiency
Bronchiectasis + infertility
Lung disease + liver disease

Screening Decision Pathway

When to consider genetic testing for pulmonary presentations

        graph TD
          START["Patient Presents with\nPulmonary Concerns"] --> SCREEN{"Screen for\nRed Flags"}
          
          SCREEN --> RF1["Failed respiratory or oxygenation newborn screens"]
          
          SCREEN --> RF2["Low nasal nitric oxide on PCD screening"]
          
          SCREEN --> RF3["Spirometry abnormalities in children without asthm..."]
          
          
          RF1 --> EVAL{"Multiple\nFlags Present?"}
          
          RF2 --> EVAL{"Multiple\nFlags Present?"}
          
          RF3 --> EVAL{"Multiple\nFlags Present?"}
          
          EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
          EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
          TEST --> DX["Molecular Diagnosis\n47-80% yield"]
          style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
          style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
          style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
        

Screening Red Flags

Findings on routine screening that may indicate genetic etiology

  • Failed respiratory or oxygenation newborn screens
  • Low nasal nitric oxide on PCD screening
  • Spirometry abnormalities in children without asthma

Exome / Genome Sequencing Indications

Clinical scenarios supporting ES/GS as a diagnostic approach

  • Chronic lung disease (CF/PCD/surfactant defects) with nondiagnostic standard testing
  • Bronchiectasis with infertility
  • Syndromic pulmonary disease

Key Evidence

Published studies supporting genetic testing for pulmonary conditions

Study Year Type Sample Yield Key Finding
Diagnosis of Primary Ciliary Dyskinesia. An Official America... 2018 Guideline None 80% Extended genetic panels (>12 genes) for PCD achieved 80% sensitivity; 54.8-93.9%...
Robust diagnostic genetic testing using solution capture enr... 2014 Cohort 20 42% 42% diagnostic yield for PCD using targeted exome capture and novel bioinformati...
Whole-Exome Sequencing and Targeted Copy Number Analysis in ... 2015 Cohort 45 76% 76% overall diagnostic yield combining WES with targeted CNV analysis in 45 PCD ...
Enhanced diagnostic yield in Meckel-Gruber and Joubert syndr... 2016 Cohort 26 46% 46% diagnostic yield in ciliopathy (Joubert/Meckel-Gruber) families with exome s...
Clinical and genetic spectrum in 33 Egyptian families with s... 2020 Cohort 33 70% 70% diagnostic yield with targeted NGS panel in 33 Egyptian PCD families, identi...
PulmZoom: Yield for Targeted Gene Panels in Genetically-Medi... 2025 Cohort None 4.1% 4.1% definitive diagnostic yield across 416 subjects with ILD, mucociliary clear...
Noncoding DNA Variants Increase the Genetic Diagnostic Yield... 2025 Cohort 496 46.8% 46.8% baseline yield in 496 PCD families; noncoding variant analysis added 38.1%...
Updated: 2026-02-24 Curated by: human Status: human reviewed