Transbronchial biopsy is performed by pulmonologists to diagnose focal and diffuse lung diseases. Compared with open lung biopsy, transbronchial biopsy has lower morbidity and mortality. Biopsy of the lung was performed by means of open surgical methods until 1963, when Anderson performed bronchoscopic lung biopsy with a rigid bronchoscope. In 1974, Levin et al published their experience with transbronchial biopsy using flexible bronchoscopy. This approach has two main rare complications: pneumothorax and severe pulmonary bleeding.
Advances in technology are leading to improved yields with fewer complications. Endobronchial ultrasonography (EBUS)-guided needle aspiration can be used for mediastinal lymph nodes if these are present and can replace transbronchial biopsy, especially for suspected sarcoidosis. Cryobiopsy of the lung provides a larger specimen without crush artefacts and may replace open lung biopsy.
Current technology includes three-dimensional (3D) preprocedural computed tomography (CT) planning, radial ultrasonography (with a small fiber), and possibly navigational bronchoscopy. Dual bronchoscopy, with one bronchoscope for cryobiopsy and a second with a balloon-tip catheter, will avoid pneumothorax and massive bleeding. [1, 2]
Transbronchial biopsy is employed in the settings of neoplastic disease, suspected sarcoidosis or hypersensitivity pneumonitis, interstitial lung disease,  pulmonary infection, unusual and unclear lung disease, and lung transplantation.
Transbronchial biopsy is commonly used to determine the etiology of lung nodules and masses. Its diagnostic accuracy increases when the nodule is larger than 2 cm, when the presence of a bronchus leading to the nodule is found on CT of the chest (positive bronchus sign), and when the tissue is repeatedly sampled. The yield of transbronchial biopsy is also high in bronchoalveolar carcinoma and lymphangitic spread of the tumor.
The diagnostic yield of this procedure can be significantly increased (to 73%) by combining flexible bronchoscopy with CT guidance in a dedicated low-dose protocol.  In another study, the sensitivity of transbronchial biopsy for a solitary pulmonary nodule was 62.2% with multislice CT guidance, compared with 52.6% with fluoroscopic guidance.  However, this technique is not cost-effective and has not been frequently used.
Transbronchial biopsy may not be reliable for heterogeneous lung diseases such as usual interstitial pneumonia. [6, 7] However, it has a high diagnostic yield for sarcoidosis: Sensitivity ranges from 50% to 85% in stage 1 disease and is higher if the parenchyma is involved. At least four to six biopsies are required for optimal diagnosis of sarcoidosis.  Transbronchial biopsy is also highly sensitive in diagnosing pulmonary alveolar proteinosis, Langerhans cell histiocytosis, eosinophilic pneumonia, lipoid pneumonia, drug-induced pneumonitis, and miscellaneous lung disease.
Transbronchial biopsy is indicated in the diagnosis of pulmonary infections in the immunocompromised patient. Although most pulmonary infections can be diagnosed by performing a bronchoalveolar lavage, transbronchial biopsy increases the diagnostic yield and rules out noninfectious causes. In particular, transbronchial biopsy increases the diagnostic yield for Pneumocystis jiroveci (carinii) pneumonia in patients with cancer, bone marrow transplant recipients, and those receiving immunosuppressive drugs. [9, 10]
Transbronchial biopsy is used in the diagnosis of allograft rejection in lung transplantation.
EBUS-guided needle aspiration is increasingly used to diagnose sarcoidosis. Cryobiopsy is used for interstitial lung disease (eg, suspected pulmonary fibrosis). A retrospective analysis by Ussavarungsi et al found transbronchial cryobiopsy to have a 51% diagnostic yield in the setting of diffuse parenchymal lung disease. 
Absolute contraindications for transbronchial biopsy include medical instability, severe hypoxia, status asthmaticus, lack of patient cooperation, malignant arrhythmia, massive hemoptysis, and uncorrectable bleeding diathesis.
Relative contraindications include the following:
Thrombocytopenia - Use caution when the platelet count is less than 50,000/μL
Uremia - A danger of serious hemorrhage exists, even in the presence of normal coagulation parameters; biopsies may be done carefully, preferably soon after dialysis or administration of desmopressin (DDAVP) and cryoprecipitate
Mechanical ventilation - The benefits of transbronchial biopsy should be weighed against the risk of developing tension pneumothorax
Pulmonary hypertension - Recommendations from the British Thoracic Society (BTS) suggest that transbronchial biopsy should be performed with caution in patients with elevated pulmonary arterial pressures
Risk of arrhythmia - The BTS recommends oxygen supplementation to keep the blood oxygen saturation above 90% and thereby minimize the risk of cardiac arrhythmia during and after bronchoscopy
Certain drugs - Aspirin can be continued if indicated, but clopidogrel is discontinued at least 5 days before the procedure; the BTS recommends discontinuing warfarin 3 days before the procedure and suggests that an international normalized ratio (INR) lower than 1.5 is safe; heparin is discontinued 6 hours before the procedure; therapeutically dosed enoxaparin is discontinued 24 hours beforehand, whereas enoxaparin given for prophylaxis of deep vein thrombosis prophylaxis is discontinued on the morning of the procedure
Certain technical considerations may improve the diagnostic performance of transbronchial biopsy and reduce the incidence of complications. Twisting the forceps as opposed to pulling may decrease bleeding (unpublished expert opinion). Not suctioning after bleeding will stop bleeding faster.
The number of biopsy specimens required for optimal diagnostic yield has been reported to be four to 10.  The 2013 BTS guidelines recommend that at least five samples should be obtained in cases where endobronchial tumor is visible and that at least five or six samples should be obtained in cases of interstitial lung disease; fluoroscopy should be employed with transbronchial biopsy in cases of localized or focal parenchymal lung disease. 
Transbronchial biopsy with fluoroscopy has not been associated with a significantly lower incidence of pneumothorax than biopsy performed without fluoroscopy.  The use of fluoroscopy during transbronchial biopsy has been shown to increase the diagnostic yield in focal lesions,  though it has not been found to provide a comparable benefit in diffuse lung diseases such as sarcoidosis. 
A comparison of transbronchial biopsy specimen yield between the use of standard-sized forceps and the use of large forceps found no significant differences in the size of the biopsies or in the amount of alveolar tissue collected.  The use of large forceps does prevent effective suctioning of secretions. In 2008, Casoni et al reported that the use of large biopsy forceps to perform transbronchial biopsy via a rigid bronchoscope significantly increased the diagnostic yield in diffuse infiltrative lung disease. 
The tissue samples obtained by means of transbronchial biopsy forceps are small (~3 mm). Therefore, this procedure is less useful in diagnosing heterogeneous lung diseases such as idiopathic interstitial fibrosis.
Combining suction catheter aspiration with forceps biopsy for bronchoscopic tissue sampling results in a higher diagnostic yield than use of either method by itself. 
Optimal sedation, adequate topical anesthesia, and proper technique all reduce the incidence of complications related to the procedure (see Periprocedural Care and Technique). The use of fluoroscopy equipment before the procedure may increase the diagnostic yield and provide a statistically insignificant decrease in pneumothoraces. The presence of an additional pulmonologist, intensivist, or anesthesiologist for sedation is likely to decrease complications. Appropriate expertise for managing pneumothorax and massive bleed must be available for rare emergencies, including balloon catheters and chest tubes.