Haemoglobin electrophoresis can confirm the diagnosis of a haemoglobinopathy, for example, sickle cell disease. Sickle cell crisis can result in an acute, life‐threatening chest syndrome, which is discussed in Chapter 17. Haemoglobinopathies are a common cause of pulmonary hypertension, which is discussed in Chapter 11.

The white cell count may be elevated in patients with an acute infection, such as upper or lower respiratory tract infection, and acute sinusitis. The differential cell count can give important clues as to the underlying condition. The neutrophil count may be increased with bacterial infections, steroid therapy, and inflammatory diseases. The white cell count may be reduced with bone marrow suppression secondary to chemotherapy and with severe infection. Patients with neutropenia are at increased risk of respiratory tract infections. Neutropenia with a neutrophil count of less than 1 mmol/L predisposes to life‐threatening sepsis.

A raised lymphocyte count in peripheral blood may be due to viral infection or Mycobacterium tuberculosis (MTB) infection. A low CD4 lymphocyte count is associated with human immunodeficiency virus (HIV) which predisposes to several respiratory tract infections, including pneumocystis jerovicii and is discussed in Chapter 8. Peripheral blood eosinophilia could be due to asthma, allergic conditions, eosinophilic granulomatosis with polyangiitis (EGPA) and parasitic infections. Causes of eosinophilia are discussed in Chapter 7.

A raised C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) can occur with any systemic infection, but may be raised with other inflammatory conditions, including rheumatological conditions and malignancy. Blood cultures should be taken in any patient who presents with symptoms and signs of sepsis, including those with severe community or hospital acquired pneumonia.

Measurements of urea, creatinine, and electrolytes are routinely done. Hyponatraemia may be associated with a syndrome of inappropriate anti‐diuretic hormone (SIADH) which may be associated with small cell lung cancer (Chapter 9). Renal failure can occur in several respiratory/renal syndromes; eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) and Goodpasture’s syndrome. If these conditions are suspected, anti‐neutrophil cytoplasmic antibodies (ANCA) should be checked. These vasculitic conditions are discussed in Chapter 11. Patients with parenchymal lung disease of unknown cause or with CT showing non‐specific interstitial pneumonia (NSIP) should have investigations for collagen vascular diseases, which will include an autoantibody screen. Liver function tests must be monitored in patients on antifungal drugs, such as itraconazole and voriconazole, and those on Azithromycin when used as a prophylactic antibiotic. Transient increase in alanine transaminase and alkaline phosphatase are often found in patients taking antibiotics.

A d‐dimer test is often done as one of the investigations for suspected pulmonary embolus (PE), but this has low specificity as it is raised in many conditions, including malignancy, infection, and pregnancy. Therefore, it is only useful when it is negative. The role of d‐dimer in diagnosing a PE is discussed in Chapter 11. Troponin levels may be elevated in severe PE because of right heart strain.

Raised corrected calcium is commonly seen in patients with lung cancer who have metastases to bone, and in squamous cell lung cancer due to exogenous parathormone secretion (see Chapter 9). Raised corrected calcium is seen in 10–20% of patients with active sarcoidosis because activated macrophages in the lung and lymph nodes synthesise vitamin D which increases calcium absorption in the gut. Patients with active sarcoidosis may have raised serum angiotensin converting enzyme (ACE) levels. This is not diagnostic of sarcoidosis but can be useful when monitoring response to treatment. Sarcoidosis is discussed in Chapter 7.

Various immunological tests are used to determine if there is immune deficiency in adults and children presenting with recurrent respiratory infections. Patients with bronchiectasis should have measurements of their immunoglobulins, including IgG subclasses (see Chapter 12). Mannose‐binding lectin deficiency and defective anti‐pneumococcal polysaccharide antibody response can predispose to recurrent respiratory infections.

Human immunodeficiency virus (HIV) infection can be the cause of recurrent respiratory tract infections and increases the risk of Mycobacterium tuberculosis infection. It is recommended that patients presenting with frequent or recurring respiratory infections, and those presenting with Mycobacterium tuberculosis infection, have an HIV test (see Chapter 8).

Patients with allergic asthma will have raised IgE levels, and those with high levels above 700 units ml⁻¹ may benefit from treatment with Omalizumab (Xolair), a recombinant IgG1monoclonal antibody. IgE levels will also be greatly elevated in allergic bronchopulmonary aspergillosis (ABPA). In patients with asthma, a radioallergosorbent test (RAST) can be used to confirm an immune response to a specific allergen, for example, cat or house dust mite. Avian precipitants will be positive in patients who have hypersensitivity pneumonitis secondary to exposure to antigens from birds, including pigeons, parrots, and budgerigars.

Theophylline is used in the management of acute and chronic asthma and COPD, and is usually given at a dose of 400 mg daily. Theophylline has a narrow therapeutic range between 10 and 20 mg l⁻¹, with significant side effects if blood levels are high; therefore, levels should be monitored. Theophylline is metabolised in the liver by the cytochrome P450 system and therefore drug interactions are important (see Chapter 3).

A lymphoproliferative disorder is always in the differential diagnosis in patients presenting with lymphadenopathy, including bilateral hilar lymphadenopathy and an anterior mediastinal mass (see Chapter 16). In lymphoma, lactate dehydrogenase (LDH) will be increased. Tumour markers too may be helpful in the investigation of an anterior mediastinal mass. The β‐human chorionic gonadotrophin (β‐hcg) level may be elevated in those with a teratoma, which could be one of the causes of an anterior mediastinal mass (see Chapter 16).

A gamma‐interferon test (QuantiFERON) is an important investigation in the diagnosis of Mycobacterium tuberculosis. This is discussed in Chapter 8.

There is evidence that Vitamin D is important in protecting against respiratory tract infections, including MTB infection. Measurement of 1, 25‐dihydroxycholecalciferol levels, the active form of the vitamin, should be done in patients with recurrent infections and in those diagnosed with MTB. Supplementation should be offered to those found to have levels less than 50 nmol l⁻¹.

Arterial blood gas (ABG) measurements are essential in managing many respiratory conditions which present with respiratory failure. The interpretation of ABG is discussed in Chapter 13.

Sputum tests can be useful in the diagnosis of respiratory tract infections. Routine sampling of sputum is not recommended in the diagnosis of community acquired pneumonia (CAP) as there is a huge variation in the rate of positivity, from 10–80%. Staphylococcal aureus is easily cultured but haemophilus influenzae is harder to culture. If MTB is suspected, then three samples of sputum should be sent for acid‐alcohol‐fast bacilli (AAFB) and Ziehl‐Neelsen (ZN) stain. If the patient is unable to cough up sputum or is unfit for bronchoscopy, induced sputum can be obtained by getting the patient to inhale hypertonic saline solution which will liquefy the secretions and cause violent coughing. Healthcare workers carrying out this procedure should take adequate precautions by doing it in a negative pressure room and by wearing masks, gowns, and gloves.

Analysis of pleural fluid is an important investigation in the diagnosis of pleural disease and is discussed in detail in Chapter 10. Pleural fluid obtained by aspiration or from pleural drainage must be sent for biochemistry (protein, lactate dehydrogenase and cholesterol), cytology, microbiology, and pH. An exudate suggests that the fluid is secondary to infection or malignancy and further investigations, such as a pleural biopsy, may be required. Tuberculous pleural effusion can be difficult to diagnose because there are very few organisms in the fluid, but a lymphocytic pleural fluid suggests MTB infection. Measurement of polymerase chain reaction (PCR), adenosine deaminase, and interferon‐y levels in pleural fluid can be diagnostic of a Mycobacterium tuberculosis pleural infection. Adenosine deaminase levels above 40 U l ⁻¹ is strongly suggestive of MTB. The pH of the fluid can be helpful in the diagnosis of an empyema.

Analysis of cerebrospinal fluid (CSF) for protein, glucose, ZN stain, and culture should be done in patients presenting with miliary tuberculosis as it is essential to diagnose tuberculous meningitis (see Chapter 8). The CSF may appear turbid, with elevated protein and lymphocytes and a very low glucose. Organisms are not often seen in the CSF, but PCR of CSF may be helpful if MTB is suspected.

Measurement of legionella and pneumococcal antigens in the urine of those presenting with CAP is recommended in the NICE guidelines and can guide management (see Chapter 8). This is a specific and sensitive test which remains positive even after treatment with antibiotics has been commenced. Three early morning urine samples are often sent for the diagnosis of MTB, but the yield is low except in genitourinary tuberculosis. Compound 490 may be present in the urine samples of patients with MTB, but further evaluation is required before this test becomes widely available.

Some 30–50% of patients with active sarcoidosis have hypercalciuria which can be measured by collecting a urine sample for 24 hours. If untreated, this may result in renal calculi and nephrocalcinosis. Patients with sarcoidosis who have hypercalcaemia and hypercalciuria may require immunosuppression.

A skin prick test is useful in patients suspected of having an atopic condition, such as asthma, eczema, or urticaria. It is a quick, safe, and inexpensive test compared to measuring allergen‐specific immunoglobin E (IgE). A few drops of purified allergen extract are placed on the flexor surface of the forearm and the tip of a small stylet is pressed into the superficial epidermis through the drop of allergen. A positive reaction is when there is a weal with a surrounding erythematous flare after 15 minutes, and the size of this can be measured in millimetres. The reaction to the allergen is compared to the reaction from a drop of histamine (the positive control) and to a drop of normal saline control solution. An itchy weal will develop at the site of histamine within 10 minutes. This is demonstrated in the supplementary material (www.wiley.com/go/Paramothayan/Essential_Respiratory_Medicine).

The Mantoux test, also known as the tuberculin sensitivity test (TST), is a well‐established investigation for suspected MTB and latent tuberculosis. Thus, 0.1 ml of purified protein derivative (PPD) is injected intradermally in the forearm of the patient and the size of the induration is measured after 48–72 hours. Individuals who have had the BCG vaccination will show a mild skin reaction at the site of injection. The Mantoux test is demonstrated in the supplementary material. The result of the Mantoux test must be interpreted carefully together with the results of the Interferon gamma release assay (IGRA), the clinical presentation of the patient, and the CXR, as discussed in Chapter 8.