Assessment of persistent pulmonary infiltrate

CRP helps distinguish community-acquired pneumonia from other causes of lower respiratory tract infection.[84] Ebell MH, Bentivegna M, Cai X, et al. Accuracy of biomarkers for the diagnosis of adult community-acquired pneumonia: a meta-analysis. Acad Emerg Med. 2020 Mar;27(3):195-206.Full text| Abstract

Urinary antigen testing is useful for diagnosing pneumococcal pneumonia in adults.

Samples are collected in the form of sputum or throat swabs.

Most cases are caused by bacteria, especially aerobic gram-negative bacilli, such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter species.

Further testing should be performed when sputum cytology is non-diagnostic and suspicion of lung cancer remains.[85] Detterbeck FC, Lewis SZ, Diekemper R, et al. Executive summary diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013 May; 143(5 Suppl):7S–37S.| Abstract

Evidence of unrecognised pulmonary tuberculosis (TB) or evidence of old healed TB (e.g., upper lobe fibrosis) may be present; such abnormalities should prompt sputum collection for smear, culture, and nucleic acid amplification testing.

Testing of 3 specimens (minimum 8 hours apart, including an early morning specimen) is recommended in many countries; consult local guidance.[86] Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):e1-33.Full text| Abstract ​Sputum specimen should be tested in patients with suspected extrapulmonary TB, as active pulmonary TB is seen in 15% to 20% of patients with extrapulmonary TB.[87] Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82.Full text| Abstract[88] Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78.| Abstract[89] Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62.Full text| Abstract

Culture of Mycobacterium tuberculosis typically takes several weeks (up to 8), decisions on treatment are usually made before culture results are known.​​

NAAT should be performed on at least one respiratory specimen when a diagnosis of pulmonary TB is being considered. NAAT may speed the diagnosis in smear-negative cases and may be helpful to differentiate non-tuberculous mycobacteria when sputum is acid-fast bacilli smear positive but NAAT negative.[68] Centers for Disease Control and Prevention. Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis. Jan 2009 [internet publication].Full text Genotyping might be considered useful in outbreaks of TB to identify transmission of TB, especially when contact had not been appreciated in the course of epidemiological investigations.

Several rapid NAATs are available for the diagnosis of TB and some are also able to detect genes encoding resistance to TB drugs.[90] World Health Organization.​ WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].Full text​​​​ 

Bronchoalveolar lavage may be indicated in patients in whom sputum induction is unsuccessful or in whom smear and NAAT are negative. Bronchoscopy is useful when other diagnoses are strongly considered or in patients in whom pulmonary TB is still suspected after other methods proved non-diagnostic.

Transbronchial lung biopsies are useful in the diagnosis of miliary disease as granulomas may be visible.

One Cochrane review found the lateral flow urine lipoarabinomannan (LF-LAM) assay to have a sensitivity of 42% in diagnosing TB in HIV-positive individuals with TB symptoms, and 35% in HIV-positive individuals not assessed for TB symptoms.[91] Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420.Full text| Abstract [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in symptomatic HIV‐positive adults?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2824/fullShow me the answer [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in unselected HIV‐positive adults (symptomatic or asymptomatic)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2825/fullShow me the answer​​​​ The World Health Organization recommends that LF-LAM can be used to assist in the diagnosis of active TB in HIV-positive adults, adolescents, and children with signs and symptoms of TB, or in those with advanced HIV or who are seriously ill.[90] World Health Organization.​ WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].Full text

Culture would still be required for drug susceptibility testing (DST).

Bronchiectasis can be seen in chronic cases. Haemoptysis usually originates from bronchial arteries, but Rasmussen's aneurysms from a pulmonary artery adjacent to a cavity can be the source of bleeding.

Residual bronchiectasis from old TB can cause haemoptysis.

Always send a sputum sample for culture where possible. Anaerobes are difficult to culture and require a specimen from the distal lung. Results may guide antibiotic therapy if organism identification and sensitivities are available.

A common sampling technique is bronchoalveolar lavage. Bronchoscopic-protected specimen brush samples, the method whereby one obtains anaerobic cultures, are not commonly performed in clinical practice.

p24 protein is present during high viral replication and so is detectable in the blood during acute infection and again during late stages of infection. Its use, therefore, is as a supplementary test during the window period and is part of fourth-generation assays indicated by the US Centers for Disease Control and Prevention for routine HIV testing.[92] Centers for Disease Control and Prevention. Laboratory testing for the diagnosis of HIV infection : updated recommendations. Jun 2014 [internet publication].Full text

In chronic or recurrent embolus there is redistribution of blood from the normal lung areas (mosaic attenuation); however, this finding is not pathognomonic. It may be an indicator of pulmonary hypertension.

A low plasma BNP level (<100 ng/L or <100 picograms/mL) can rapidly rule out decompensated heart failure (HF) and point to a pulmonary cause. A high plasma BNP level (>400 ng/L or >400 picograms/mL) strongly supports the diagnosis of abnormal ventricular function (i.e., HF). Intermediate values (100-400 ng/L or 100-400 picograms/mL) fall into the so-called 'grey zone' and should spur a search for a potential non-cardiac cause of dyspnoea: for example, COPD.

Regional wall motion abnormalities, valve disease, and cardiomyopathies can be estimated.

Direct observation of the foreign body. Mucosal inflammation and granulation tissue may exist. Post-obstructive infections are possible.

Often normal in non-fibrotic sarcoidosis; may not reflect disease activity or symptom burden.[93] Thillai M, Atkins CP, Crawshaw A, et al. BTS clinical statement on pulmonary sarcoidosis. Thorax. 2021 Jan;76(1):4-20.Full text

CD4/CD8 ratio >3.5 supports the diagnosis with a sensitivity of 53% and a specificity of 94%.[94] Statement on sarcoidosis. Joint statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS board of directors and by the ERS executive committee, February 1999. Am J Respir Crit Care Med. 1999 Aug;160(2):736-55.Full text

Anti-Scl 70, antinuclear antibody, rheumatoid factor, anti-Jo antibody, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibody, precipitin.

Other non-pathognomonic signs may include peripheral subpleural, basal honeycombing in interstitial pulmonary fibrosis; cysts in lymphangioleiomyomatosis and lymphocytic interstitial pneumonitis, histiocytosis X, and Sjogren's syndrome; bilateral patchy consolidation, subpleural, basal, peribronchial distribution, and nodules in organising pneumonia; ground-glass with airspace consolidation and fibrosis in acute interstitial pneumonitis (diffuse alveolar damage).[95] Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-47.Full text| Abstract

Non-specific but helpful in assessing severity.

Helps to narrow the differential diagnosis. Transbronchial biopsy is especially helpful in sarcoidosis, eosinophilic pneumonia, Goodpasture's syndrome, and histiocytosis X.

Histological abnormalities alone are rarely specific: careful clinical, radiological, and pathological correlation is necessary for diagnosis.

Helps determine the severity of the disease.

ANA usually ≥1:160. Currently the most sensitive test for confirming the diagnosis of SLE when accompanied by typical clinical findings. A positive ANA in itself is not diagnostic as it may be positive in other connective tissue diseases and in patients treated with certain drugs such as procainamide, hydralazine, isoniazid, and chlorpromazine.

Pulmonary infiltrates in acute lupus pneumonitis and diffuse alveolar haemorrhage.

Elevated diffusion capacity is suggestive for pulmonary haemorrhage.

Restrictive defect depends on the severity of lung involvement (interstitial lung disease, organising pneumonia, shrinking or vanishing lung syndrome).

If pulmonary hypertension is suspected (especially if antiphospholipid antibodies are present).

Bronchoalveolar lavage may aid in excluding an infection.

Frequent finding in active SLE.

Interstitial lung fibrosis more often in patients with anti-topoisomerase-I (Scl-70).

Pulmonary hypertension more often in patients with anti-centromere and U3-RNP antibodies.

Patients with diffuse cutaneous systemic scleroderma are at an increased risk of developing interstitial lung disease early, but patients with limited cutaneous disease can also develop the condition.

Dilatation of oesophagus common.

Drug-induced lung disease should be considered.

Interstitial lung disease: reduced lung volumes and reduced DLCO.

Pulmonary arterial hypertension: decrease in DLCO in the absence of significant lung volume abnormalities.

Patients with limited cutaneous systemic scleroderma often develop pulmonary arterial hypertension with or without interstitial lung disease.

Bronchoalveolar lavage may aid in excluding an infection.

MSAs and MAAs are found in most patients with dermatomyositis. They are increasingly used in clinical practice, although are not widely available.[96] Kohsaka H, Mimori T, Kanda T, et al. Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists, neurologists and dermatologists. Mod Rheumatol. 2019 Jan;29(1):1-19.| Abstract

MSAs and MAAs are found in most patients with dermatomyositis. They are increasingly used in clinical practice, although are not widely available.[96] Kohsaka H, Mimori T, Kanda T, et al. Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists, neurologists and dermatologists. Mod Rheumatol. 2019 Jan;29(1):1-19.| Abstract

Similar in both eyes.

Corneal damage.

May be normal.

Interstitial lung disease is the most common pulmonary abnormality (e.g., lymphocytic interstitial pneumonitis, non-specific interstitial pneumonitis).

Enlarged lymph nodes especially in patients with primary systemic scleroderma.

More sensitive than chest x-ray in identifying interstitial fibrosis and therefore is useful when a patient has symptoms or abnormalities of pulmonary testing but their chest x-ray is normal.

Characteristic endobronchial lesions often associated with concomitant parenchymal involvement. Bronchoscopic biopsies have a very low diagnostic yield, as large biopsy specimen is needed. Biopsy of respiratory tract lesions is relatively contraindicated because of the risk of bleeding.

Particularly indicated when there is clinical suspicion of substance misuse as either a cause or a contributor to diffuse alveolar haemorrhage. Blood testing for cocaine or its metabolites is typically not indicated, as symptoms do not correlate with plasma concentrations.[97] Blaho K, Logan B, Winbery S, et al. Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED. Am J Emerg Med. 2000 Sep;18(5):593-8.| Abstract

May reveal presence of additional drugs.

Goodpasture's syndrome with anti-glomerular basement membrane antibody-positive. Systemic lupus erythematosus with hypocomplementaemia, antinuclear antibody, anti-DNA. Cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA) seropositivity suggests granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis). Perinuclear ANCA (pANCA) seropositivity may occur with Churg-Strauss syndrome or microscopic polyangiitis.

Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis, collagen vascular diseases (e.g., systemic lupus erythematosus), Goodpasture's disease.

Alveolar haemorrhage with ground glass or airspace-filling opacities, focal but can rapidly progress to diffuse. Recurrent episodes may lead to pulmonary fibrosis and interstitial opacities.

Elevated diffusing capacity is suggestive of pulmonary haemorrhage.

Granulomatosis with polyangiitis presents with concomitant vasculitis and granulomatous inflammation. Vasculitis in microscopic polyangiitis cannot be distinguished from that of Churg-Strauss syndrome. Immunofluorescence microscopy demonstrates linear deposition of IgG on capillary basement membranes/kidney biopsy, a pathognomonic finding of Goodpasture’s disease.

Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis, collagen vascular diseases (e.g., systemic lupus erythematosus), Goodpasture's disease.

Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) with nodules, multiple or single, may cavitate leaving diffuse areas of lung opacity, representing pulmonary haemorrhage.

Alveolar haemorrhage with increasingly haemorrhagic fluid on sequential lavage, haemosiderin-laden macrophages.

Histological findings may exist in multiple organs: upper respiratory tract, skin, kidney, or lung.

Flow findings suggest subglottic or endobronchial airway stenosis. Diffusion findings suggest pulmonary haemorrhage.

Eosinophilia of >10% on differential white blood cell count.

Migratory or transient pulmonary opacities most common.

Lung or other affected tissue present in biopsy.

Not specific for condition.

By the time parasitic forms are found in the stool, pulmonary symptoms usually resolve.

Larvae are occasionally found at the time of pulmonary symptoms.

Helps to confirm diagnosis and is a marker of exposure, but not particularly sensitive or specific. May not be uniformly positive.

Not generally recommended because of lack of standardised antigens and trained personnel.

High levels of interleukin-5 in BAL. Diffuse alveolar damage with prominent eosinophilia is characteristic in lung biopsy.

If specimens from transbronchial biopsy are not adequate, video thoracoscopic lung biopsy or open biopsy is recommended.

Occupational pneumonia can be also found in tissue specimen.

Exclusion of other aetiologies.

Diagnosis by exclusion of other aetiologies (e.g., infections) and temporal relationship of exposure to drug and time course of lung disease.

Blood testing for cocaine or its metabolites is typically not indicated, as symptoms do not correlate with plasma concentrations.[97] Blaho K, Logan B, Winbery S, et al. Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED. Am J Emerg Med. 2000 Sep;18(5):593-8.| Abstract

May reveal presence of additional drugs.

Pneumothorax and pneumomediastinum are rare complications of cocaine use. They are probably related to the practice of some cocaine users to perform a Valsalva manoeuvre following insufflation or inhalation, not a direct effect of the drug itself. A haemorrhagic alveolitis (crack lung) rarely occurs but is well described in the literature.

Confirmation of amyloid deposits in tissue is essential for diagnosis. Amyloid fibrils identified on electron microscopy with Congo red stain or thioflavine-T.

Using serial chest CT, progression from nodules to cavitating nodules to cystic lesions can be seen.

If specimens from transbronchial biopsy are not adequate, video thoracoscopic lung biopsy or open biopsy is considered.

Airflow limitation, increased total lung capacity (TLC), increase in residual volume (RV), and RV/TLC ratio.

Transbronchial lung biopsy, open lung, or thoracoscopic biopsy may be used.

Tissue confirmation may not always be necessary if history and high-resolution CT chest are indicative.

Correlates with disease severity.

Infiltrates usually spare the periphery and are more pronounced in perihilar regions.

Indicated when lavage and transbronchoscopic biopsy are negative. Characteristic PAS-positive amorphous, granular lipoproteinaceous material filling terminal bronchioles and alveoli.