Cystic fibrosis differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2], Karina Zavaleta, MD [3], Anmol Pitliya, M.B.B.S. M.D.[4]

Overview

Cystic fibrosis has to be differentiated from other conditions with similar presentation of cough and wheeze like common cold, asthma, bronchiolitis, emphysema, primary ciliary dyskinesia (Kartagener syndrome), bronchitis, bronchiectasis, foreign body aspiration, pneumoconiosis, interstitial lung disease, cardiogenic pulmonary edema, GERD and sarcoidosis.

Cough

Cystic fibrosis must be differentiated from other diseases presenting with cough and wheeze include:

Organ system		Diseases	Clinical manifestations								Diagnosis				Other features
			Symptoms							Physical exam
			Onset	Duration	Productive cough	Hemoptysis	Weight lost	Fever	Dyspnea	Ascultation	Lab findings	Imaging	PFT	Gold standard
Respiratory	Upper airway diseases	Common Cold	Acute	3-10 days	✔	-	-	✔	-	Rales Wheezing	Bacterial culture is not indicated	Chest X-Ray in patients with signs of consolidation	Normal function	Clinical diagnosis	Conjunctival injection Nasal congestion
	Lower airway	Asthma	Chronic	Years	✔ Clear mucoid or yellow sputum	-	-	-	✔	Wheezing (expiratory) Rales Rhonchi	Eosinophilia is observed in complete blood count (CBC) Total serum IgE in test for allergy	Normal airways in chest X-ray CT if there any abnormality in chest X-Ray	FEV1/FVC ratio <70% and FEV1 >15% increase after 15 minutes of 2 puffs of beta 2 sympathomimetic drug After physical active FEV1 decreases by >15% After inhaled corticosteroid (ICS)FEV1 increased by >15%	Airflow limitation on spirometry	Family history Seasonal variation
		Acute Bronchitis	Acute	From 5 days to 1 or 3 weeks	✔	-	-	-	✔	Wheezing Rhonchi	Sputum culture is not indicated PCR in bacterial infection	Chest X-ray to exclude other diseases	FEV1 < 80%	Clinical diagnosis	Majority of cases are caused by respiratory viruses
		Chronic Bronchitis	Chronic	Most of the days for three months in the las two years.	✔ Clear sputum	-	-	✔	✔	Wheezing Rhonchi	Blood test Arterial blood gas (ABG)	Chest X-Ray to exclude other diseases CT	FEV1/FVC ratio < 70% Post bronchodilatador FEV1 > 80% Reduced FVC after bronchodilatador administration Decread vital capacity Increased total lung capacity	Demostration of airflow limitation on spirometry	Smoker's cough Cigarette smoking Pollution
		Primary Ciliary Dyskinesia (Kartagener Syndrome)	Chronic	Years	✔	✔	✔	-	✔	Wheezing Crackles	Low or absent amount of nasal nitric oxide (nNO). Mucociliary clearance may be useful for screening Confirmation with tests of ciliary function.	Chest X-ray reveals : Bronchial wall thickening. Bronchiectasis and hyperinflation. Cystic bronchiectasis with air-fluid levels may be visible. Usually involves the lower and middle lobes.	Mild to moderate obstructive ventilatory defect Not specific May be normal	Transmission electron microscopy (TEM) for assessment of ciliary ultrastructure	Recurrent respiratory infections Poor sense of smell
		Bronchiectasis	Chronic	Months to years	✔ Mucopurulent sputum	✔		-	✔	Crackles Wheezing Shortness of breath	Complete blood count (CBC) IgG, IgM and IgA Sputum culture for fungi, bacteria and mycobacteria	Linear atelectasis and dilated airways in chest X-Ray	FEV1/FVC <70% Normal FVC Low levels of FEV1	CT of chest	Digital clubbing Recurrent pleurisy
		Emphysema	Chronic	Months to years	✔ Mucoid or purulent sputum	-	-	✔	✔	Shortness of breath Wheezing Prolonged expiration Crackles	Blood test Testing for alpha 1-antitrypsin	Chest X-Ray to exclude other diseases CT	FEV1/FVC <70% Post bronchodilator FEV1 >80	Detection of early emphysema in CT of chest	Exposure of tobacco and air pollution
		Foreign body aspiration	Acute	Variable	✔	✔	-	✔	✔	Wheezing Decreased breath sounds	No specific	Hyperinflated lungs, atelectasis, and mediastinitis Shift in chest radiograph when the object is radio-opaque CT	Not specific	Bronchoscopy	In children <1 year and adults >75 years Organic materials in children Inorganic materials in adults
		Bronchiolitis	Acute	8-15 days	✔	-		✔	✔	Wheezing Crackles Increased respiratory rate	Complete blood count (CBC) Urinalysis (in infants) Urine culture ( in infants)	Chest X-Ray	Normal function or obstructive changes (FEV1/FVC <70%) Air trapping in Lung volumes Reduced Diffusing capacity of carbon monoxide ( DLCO)	Clinical diagnosis	Etiology: Respiratory syncytial virus, Rhinovirus Children <2 years
	Parenchyma	Cystic fibrosis	Chronic	Variable	✔	-	✔		✔	Barrel-shaped chest Wheezing Tachypnea	Respiratory tract culture for CF Bronchoalveolar lavage for cytology ≥ 60 mmol/L Sweat chloride test CFTR mutation in molecular testing	Hyperinflation, atelectasis, and infiltrates on chest X-Ray Severe patients present bronchietasis, "tram tracks" peribronchial cuffing in chest X-Ray The extension of bronchietasis can be defined by CT	RV/TLC ratio increased FEV1/FVC ratio <70% Low levels of FEV1 High levels of TLC RV increased	Sweat chloride test	Evidence of CFTR dysfunction
		Pneumoconioses	Acute, Chronic	Years	-	-	✔	✔	✔	Wheezing Rhonchi Crackles	Arterial blood gas Complete blood count (CBC)	Small oppacities and fibrosis observed in chest X-ray CT FDG-PET	FEV1/FVC <70% FEV1 <80%	Exposure history and chest radiograph	Fibrogenic: Silica, asbestos Inert: Iron, barium Granulomatous: Beryllium Giant cell pneumonia: Cobalt
		Interstitial lung disease	Chronic	Variable	-	✔	✔	-	✔	Wheezing Crackles or velcro rales Inspiratory high-pitched rhonchi	Test for hepatic and renal function Hematologic test in differential CBC Serological testing	Nodular, reticular or both pattern in chest X-ray CT in patients with diffuse pulmonary lung disease	Reduction in FVC, RV, FRC, TLC and FEV1 on spirometry FEV1/FVC normal or increase Lung volumes Diffusion capacity (DLCO reduced)	Lung biopsy when lab, imaging, and PFT has indeterminate result	Clubbing is common in asbestosis and idiopathic pulmonary fibrosis
Cardiac		Cardiogenic pulmonary edema	Acute	Days to weeks	✔ Pink frothy, liquid	-	✔	-	✔	Crackles Increased respiratory rate Wheezing Rhonchi Gurgling sounds	Arterial blood gas BUN Serum creatinin Serum troponin Electrolytes Lactic acid Complete blood count	Cardiomegaly, pleural effusion, interstitial edema, alveolar edema and blood redistribution in lower lobes in chest X-ray	Not specific	Clinical diagnosis Tests are supportive	12-lead ECG Plasma BNP and NT-proBNP Echocardiography
Gastrointestinal		Gastroesophageal reflux	Chronic	Variable	✔	-	✔	-	✔	Wheezing Hoarseness	Not specific	Upper endoscopy Barium esophagram	Normal function	PH testing	--
Autoinmune		Sarcoidosis	Chronic	Years	-	-	✔	✔	✔	Wheezing Squeaky sounds	Complete blood count (CBC) Urinalysis BUN Liver function test Calcium Alkaline phosphatase levels Electrolytes Histopathologic detection	On chest X-Ray: Stage 1: Bilateral hiliar adenopathy Stage 2: Reticular opacities and hiliar adenopathy Stage 3: Shrink hiliar nodules and reticular opacities Stage 4: Lost of volume	Reduced FVC Decreased of TLC	Clinical diagnosis, histopathologic detection of noncaseating granulomas and exclusion of other diseases	Young adults Skin, joint and eye lesions