Fig. 8.1 Differing responses to varying concentrations of histamine.
Airway hyperresponsiveness test or histamine/methacholine challenge test
Pleural aspiration (diagnostic)
Epworth test/Epworth sleepiness scale
Flow–volume loops/maximum expiratory flow–volume curve
Sputum microscopy and culture/sputum cytology
Suspected asthma in patients with normal spirometry.
1.Explain the procedure to the patient.
3.Warn that wheezing and shortness of breath (SOB) may occur and that a bronchodilator may be given.
5.Patient breathes in a nebulized aerosol of histamine (or methacholine) of ↑ concentrations. This stimulates bronchoconstriction in a dose-dependent manner.
6.The FEV1 is measured after each dose.
7.Patient must remain in the department for 30min following the procedure to observe any delayed reactions.
The percentage fall in FEV1 from baseline is plotted against the dose of inhaled histamine on a logarithmic scale. A dose–response curve is constructed, and the provocation concentration (PC) of inhaled histamine required to reduce the FEV1 by 20% (PC20) can be derived by linear extrapolation. This figure has been arbitrarily chosen to assess degrees of bronchial reactivity for ease of comparison and safety.
•Asthma suggested by PC20 <8mg/mL (see Fig. 8.1).
•A direct relationship exists between the severity of asthma and requirement for medication, and the PC20 value as an index of bronchial hyperresponsiveness.
•Non-asthmatic subjects almost always have a PC20 >8mg/mL.
•Safe—bronchoconstriction may be reversed by an inhaled β-adrenergic agonist. It is important that personnel performing the test are able to recognize severe bronchospasm and that resuscitation equipment is available.
•Documented cholinergic hypersensitivity, e.g. cholinergic urticaria or angio-oedema, or both.
•Allergy to histamine/methacholine.
•Inability to perform acceptable-quality spirometry.
•Unstable cardiac status, e.g. recent MI, arrhythmia, or heart failure.
•Uncontrolled hypertension (systolic BP >200 or diastolic BP >100).
•Severe baseline obstruction with FEV1 <80% predicted or <1.5L.
•PEFR chart: diurnal variation.
•Sputum cytology: eosinophilia.
•Exhaled nitric oxide (NO): elevated levels.
•Bronchial hyperresponsiveness in asthma is not a static phenomenon and may vary widely from day to day.
•May change quite markedly without any change in symptoms (and vice versa).
•Represents only one component contributing to the symptomatology of asthma. Others include airway oedema and mucus hypersecretion.
Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and exercise challenge testing–1999. Am J Respir Crit Care Med 2000; 161: 309–29.
Joos GF, O’Connor B. Indirect airway challenges. Eur Respir J 2003; 21: 1050–68.
Lotvall J, Inman M, O’Byrne P. Measurement of airway hyperresponsiveness: new considerations. Thorax 1998; 53: 419–24.
Pratter MR, Irwin S. The clinical value of pharmacologic bronchoprovocation challenge. Chest 1984; 85: 260–5.
Smith CM, Anderson SD. Inhalation provocation tests using nonisotonic aerosols. J Allergy Clin Immunol 1989; 84: 781–90.
•Breathlessness (acute or chronic).
•Acute asthma with O2 saturation <92% (on air).
OHCM 10e, p. 189, p. 665.
•Informed consent (verbal usually satisfactory).
•Common sites: radial/brachial/femoral arteries.
•Absent ulnar circulation (Allen’s test).
•Arteriovenous (AV) fistula for dialysis.
•Presence of graft/extensive vascular disease.
2.Clean the skin with an alcohol swab.
3.Confirm the position of maximum pulsation with the non-dominant hand.
5.Insert a 23G needle attached to a heparinized 2mL syringe.
6.If using low-resistance syringe, this will fill automatically; otherwise aspirate gently.
7.Remove the needle, and apply firm, gentle pressure with a cotton wool ball for 5min.
•Metabolic acidosis vs compensation.
OHCM 10e, p. 162, p. 189, p. 771.
Start by looking at the pH. Next check whether CO2 fits with the pH change; if so, the 1° problem is respiratory. Then check for any metabolic compensation or for a combined respiratory and metabolic process. If CO2 is not consistent with the pH change, the 1° disturbance is metabolic and you should check whether there is any respiratory compensation. To assess oxygenation properly, it is essential to record the patient’s inspired O2 concentration (FiO2) at time of sampling.
•No real alternative for assessing CO2 or acid–base balance.
•Greater precision in upper ranges of arterial O2 saturation (SaO2) curve (see Fig. 8.2).
•Pulse oximetry: gives indication of oxygenation status, but not CO2 levels.
•If the sample is to be analysed in a laboratory with >5min transit time, it should be kept on melting ice to slow the metabolic activity of the cells.
•Avoid arterial puncture, if possible, in patients on anticoagulant therapy, those with bleeding disorders, or those who have received thrombolytics in previous 24h.
•Failure to note the FiO2 at time of sampling will lead to difficulty in interpretation and potential therapeutic errors.
Carruthers DM, Harrison BD. Arterial blood gas analysis or oxygen saturation in the assessment of acute asthma? Thorax 1995; 50: 186–8.
Syabbalo N. Measurement and interpretation of arterial blood gases. Br J Clin Pract 1977; 51: 173–6.
•Unilateral pleural effusion detected clinically and with imaging, e.g. CXR, USS, CT chest.
•Aspiration should not be performed routinely for bilateral pleural effusions if a transudate is suspected.
3.Posterior or axillary approach if effusion large (be guided by bedside USS).
4.Clean skin with antiseptic solution.
5.Infiltrate with LAn (1% lidocaine).
6.Insert a fine-bore 21G (green) needle attached to a 50mL syringe under USS guidance. Note: ensure the needle enters immediately above the rib to avoid the neurovascular bundle.
7.Aspirate fluid. If no fluid, then try adjusting the angle of the needle with USS guidance.
•Pleural fluid is normally straw-coloured and odourless.
•Pleural fluid analysed for protein, glucose, LDH, microbiology, cytology, and pH.
•If heavily bloodstained, suspect malignancy, pulmonary infarction, or trauma. A traumatic tap will become progressively less bloodstained.
•If creamy, opalescent fluid: chylothorax (lymphoma, trauma to the thoracic duct, yellow nail syndrome, lymphangioleiomyomatosis) or pseudo-chylothorax, e.g. in TB or RhA.
Measure blood LDH and total protein simultaneously for Light’s criteria; satisfying any ONE criterion means it is exudative:
•Pleural total protein/serum total protein >0.5.
•Pleural LDH > two-thirds of upper limit of normal for serum LDH.
(See Table 8.1.)
•Provides cytological, microbiological, and biochemical data.
•Thoracoscopy (medical or surgical).
•May be difficult to locate a loculated effusion, even with USS.
•Visceral injury (e.g. liver).
•Large volumes of pleural fluid (>1000mL) should not be aspirated at one time due to risk of inducing re-expansion pulmonary oedema.
Hooper C, Lee G, Maskell N. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax 2010; 65: ii4–17.
Light RW. Diagnostic principles in pleural disease. Eur Respir J 1997; 10: 476–81.
Screening tool for OSA. Measures general level of daytime sleepiness.
1.Ask patient to fill in questionnaire.
2.Subject rates on a scale of 0–3 the chance that, as part of his usual life in recent times, he would doze in each of eight different situations.
Use the following scale to choose the most appropriate number for each situation:
•Sitting inactive in a public place (e.g. theatre or a meeting).
•As a passenger in a car for an hour without a break.
•Lying down to rest in the afternoon when circumstances permit.
•Sitting and talking to someone.
•Sitting quietly after lunch without alcohol.
•In a car, whilst stopped for a few minutes in the traffic.
Epworth sleepiness scale (ESS) score is the sum of eight item scores and can range from 0 to 24.
Clinically normal score <10. Each ESS item gives an estimate of sleep propensity in one of eight specific situations, whereas the total ESS score gives a measure of more general average sleep propensity. Does not measure ‘subjective’ sleepiness.
•Polysomnography/Visi-Lab studies.
•Maintenance of wakefulness test.
Limited by patient’s ability to read and comprehend the questionnaire and answer questions honestly.
•To confirm that reduced exercise tolerance exists.
•To determine the degree of impairment and disability.
•To investigate which system appears responsible for the reduction.
•To evaluate treatment results.
1.Evaluate the patient’s medical history for contraindications to test.
2.Warn the patient of cardiovascular complications (e.g. mortality 1:10,000 tests).
3.Obtain informed written consent.
4.Patient to wear comfortable clothes and shoes.
5.Monitoring: ECG, O2 saturation, BP.
6.Exercise: treadmill/bike/free run on flat surface.
7.Steady state 5–12min walking test (usually 6min) or stepped stress test.
8.During a maximal exercise test, the patient should be able to achieve 85–90% of predicted maximum heart rate.
•Unstable myocardium (recent MI, unstable angina, arrhythmias, severe valvular heart disease, congestive heart failure).
•Systemic hypertension (systolic >200mmHg, diastolic >120mmHg).
•Cardiac response: ECG, BP, cardiac output, and stroke volume response.
•Ventilatory response: ventilatory limitation (reduced breathing reserve), pattern of response, VT, minute volume, respiratory rate.
•Gas exchange: ABGs, A–a gradient, PaCO2.
•Ventilatory (anaerobic) threshold: normal or ↑.
•VO2max(maximum O2uptake): normal or ↑.
Useful in making the distinction between exertional dyspnoea 2° to lung disease or fatigue 2° to cardiac dysfunction. In patients known to have asthma, exercise test is +ve in 75% of cases with a single treadmill run and 97% if the test is repeated in −ve responders. A fall of 10% or more from baseline in PEFR or FEV1 suggests exercise-induced asthma.
Best assessment of exercise capacity. Adds to diagnostic accuracy quantitatively (measurement of work capacity, VO2max, and sustained work capacity) and qualitatively (identification of the cause of exercise limitation).
•For asthma: exhaled NO levels, histamine/methacholine inhalation challenges, and PEFR diary.
•Dependent on patient effort and compliance.
•Not suitable for patients with severe objective measurement of respiratory impairment.
•►Bronchospasm: usually easily reversed with an inhaled β -adrenergic agonist.
•►Cardiac arrhythmias/arrest: appropriate equipment and drugs should be available in the exercise testing area. Personnel should be trained in basic and advanced cardiopulmonary resuscitation.
Hughes JMB, Pride NB (eds.). Lung Function Tests: Physiological Principles and Clinical Applications. Philadelphia: WB Saunders, 1999.
König P. Exercise challenge: indications and techniques. Allergy Proc 1989; 10: 345–8.
Sue DY. Exercise testing in the evaluation of impairment and disability. Clin Chest Med 1994; 15: 369–87.
•Assessment of treatment response.
1.Patient breathes directly into the NO analyser.
2.Perform three tests each time, and record the largest value.
Exhaled nitric oxide fraction (FeNO) can be detected by chemiluminescence in the range of 5–300ppb.
Elevated FeNO levels are associated with eosinophilic asthma:
•<25ppb: low probability. Asthma unlikely. Consider other possible aetiologies for symptoms.
•25–50ppb: intermediate probability. Based on clinical judgement, asthma is a possible diagnosis. Consider initiating inhaled corticosteroids and monitoring further FeNO levels.
•>50ppb: high probability. Asthma likely in an appropriate clinical context. Symptomatic patients are likely to benefit from inhaled corticosteroids.
•Objective measure of response to treatment.
•Histamine/methacholine inhalation challenges.
•Sputum cytology: eosinophilia.
•A −ve FeNO does not exclude asthma; asthma may be caused by neutrophilic airways inflammation.
•FeNO levels are reduced by smoking.
Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001; 163: 1693–722.
Massaro AF, Gaston B, Kita D, Fanta C, Stamler JS, Drazen JM. Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med 1995; 152: 800–3.
National Institute for Health and Care Excellence (2012). Measuring fractional exhaled nitric oxide concentration in asthma: NIOX MINO, NIOX VERO and NObreath. Diagnostics guidance DG12. 
http://www.nice.org.uk/guidance/dg12.
Saito J1, Gibeon D, Macedo P, Menzies-Gow A, Bhavsar PK, Chung KF. Domiciliary diurnal variation of exhaled nitric oxide fraction for asthma control. Eur Respir J 2014; 43: 474–84.
•Any patient with persistent/substantial haemoptysis.
•To determine course of recurrence/persistence.
•Interstitial lung disease (ILD):
•To obtain BAL for cytology; useful in diagnosis of sarcoidosis and hypersensitivity pneumonitis.
•To obtain endobronchial biopsies (EBBs); useful in diagnosis of sarcoidosis.
•To obtain transbronchial lung biopsies (TBLBs); useful in diagnosis of sarcoidosis, hypersensitivity pneumonitis, and lymphangitis carcinomatosa.
•Spirometry. Patients with obstruction may require nebulized bronchodilators pre-procedure.
•ABGs on air if hypoxaemia suggested by O2 saturation.
1.Patient informed and consented. Fasted from solids for 6h and liquids for 3h.
2.Frontal approach with patient lying on couch, trunk at 45°.
4.Basic monitoring—pulse oximeter and BP.
5.Supplementary O2 via single nasal cannula.
6.IV sedation: midazolam/alfentanil.
7.Topical lidocaine spray to nose and pharynx.
8.Bronchoscope lubricated with 2% lidocaine gel and passed via nostril or mouth guard.
9.Further boluses of lidocaine (1%) applied to cords and bronchial tree.
•Patients at risk of pulmonary and cardiovascular decompensation, e.g. recent MI, unstable angina, arrhythmias, severe valvular heart disease, uncontrolled congestive heart failure, pulmonary hypertension, severe hypoxaemia.
•Patients at high risk of bleeding, e.g. patients on antiplatelet or anticoagulant therapy or patients with coagulopathies such as thrombocytopenia.
•Bronchoscopists should be cautious when sedating patients with COPD.
•Direct inspection of the nares, nasopharynx, and oropharynx.
•Assess movement of vocal cords (ask patient to say ‘eee’).
•Direct inspection of the bronchial tree down to subsegmental level.
•Able to take endobronchial/transbronchial biopsies and brushings. BAL: wedge the tip of the bronchoscope into a subsegmental bronchus and instil aliquots of 50mL of sterile saline into the distal airway. Aspirate immediately, aiming to obtain ~50% of instilled volume. Bronchial washings (BWs) are performed in a similar fashion with 10–20mL of sterile saline instilled into the bronchus.
(See Table 8.2.)
| Histology | ||
| Cytology | ||
| Microbiology | BAL/BW |
Some appearances diagnostic.
Screening: X-ray-guided biopsy of non-visible lesions.
•Provides histological and immunobiological confirmation (to back up CT/CXR diagnosis).
•Therapeutic—removal of retained secretions, mucus plugs, blood clots.
•Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): allows assessment and biopsy of mediastinal lymph nodes and tumours.
•Rigid bronchoscopy: under GAn:
•Allows therapeutic interventions, e.g. laser therapy, cryotherapy, stent insertion, debulking of large tumours in the major airways, and better control of haemorrhage.
•Preferable for removal of foreign body.
•Pneumothorax with transbronchial biopsies.
•Post-bronchoscopy fever with BAL (usually resolves in a few hours with paracetamol, but antibiotics may be necessary).
•If performed in a day case unit with sedation, the patient will not be able to drive home and will need a responsible adult in attendance overnight.
•Only visualizes proximal airways.
•Biopsies may be inadequate or from necrotic areas.
•Not easy to biopsy submucosal tumour.
•Needs good-quality cytology preparation.
Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults. Thorax 2013; 68: i1–44.
Yasufuku K, Nakajima T, Chiyo M, Sekine Y, Shibuya K, Fujisawa T. Endobronchial ultrasonography: current status and future directions. J Thorac Oncol 2007; 2: 970–9.
The following groups of patients should be referred to a chest physician for assessment before flying:
•Severe COPD (FEV1 <30%) or asthma.
•Severe (vital capacity (VC) <1L) restrictive disease (including chest wall and respiratory muscle disease).
•Pre-existing requirement for ventilator support or O2 therapy.
•Co-morbidity with conditions worsened by hypoxaemia (e.g. coronary artery disease, pulmonary hypertension, cyanotic congenital heart disease, cerebrovascular disease).
1.Take a history and examine the patient, with particular reference to cardiorespiratory disease and previous symptoms during flights.
3.Measure SpO2 by pulse oximeter. ABGs should be performed if hypercapnia is suspected.
4.A hypoxic challenge test (breathing 15% FiO2 for 20min via a face mask, followed by ABG sampling) may be necessary, depending on the results of the initial assessment.
(See Tables 8.3 and 8.4.)
Table 8.3 Results of initial assessment breathing air
| Screening result | Recommendation |
| Sea-level SpO2 >95% | O2 not required |
| Sea-level SpO2 92–95% and no risk factor* | O2 not required |
| Sea-level SpO2 92–95% and additional risk factor* | Perform hypoxic challenge and ABGs |
| Sea-level SpO2 <92% | In-flight O2 |
* Additional risk factors: hypercapnoea; FEV1 <50% predicted; lung cancer; lung fibrosis; kyphoscoliosis; respiratory muscle weakness; cerebrovascular or cardiac disease; within 6 weeks of discharge for an exacerbation of chronic lung or cardiac disease; recent pneumothorax; risk of (or previous) VTE disease; recent pneumothorax; and patients with previous significant respiratory symptoms associated with air travel.
Table 8.4 Results of hypoxic challenge test
| Hypoxic challenge result | Recommendation |
| PaO2 ≥6.6kPa (>50mmHg) or SpO2 ≥85% | O2 not required |
| PaO2 <6.6kPa (<50mmHg) or SpO2 <85% | In-flight O2 (flow rate 2L/min) |
PaO2, arterial oxygen tension; SpO2, oxygen saturation.
Identifies most patients requiring in-flight O2 therapy.
•In complex cases, patients may require testing in a hypobaric chamber.
•Infectious patients should not fly.
•Even with in-flight O2 therapy, travel cannot be guaranteed to be safe.
Ahmedzai S, Balfour-Lynn IM, Bewick T, et al.; British Thoracic Society Standards of Care Committee. Managing passengers with stable respiratory disease planning air travel: British Thoracic Society recommendations Thorax 2011; 66(Suppl 1): i1–30.
Coker RK, Shiner RJ, Partridge MR. Is air travel safe for those with lung disease? Eur Respir J 2007; 30: 1057–63.
Patient in whom COPD/small airways disease or upper airway obstruction is suspected.
•Advised to wear comfortable, loose clothing.
•Technician explains procedure to patient.
•Mouthpiece in position; patient breathes in maximally and then out as hard and fast as possible.
•Three acceptable manoeuvres should be performed. Patients must perform the test with maximal effort each time, and the results should be similar for each of the three attempts.
Particularly useful in recognizing patients with narrowing of the central airway (larynx and trachea). Narrowing at this site has the greatest effect on maximum expiratory flow and also on maximum inspiratory flow, giving rise to a characteristic appearance. Also identifies patients with reduced elastic recoil (bullae, emphysema) or reduced airway lumen (asthma, COPD, bronchiolitis).
Oscillation of flow gives a ‘sawtooth’ pattern. This usually signifies instability of the upper airway and has been observed in OSA, thermal injury to the airway, bulbar muscle weakness, extrapyramidal neuromuscular disorders, upper airway stenosis/tracheomalacia, and snoring.
(See Fig. 8.3.)
•Allows early detection of small airway disease—more sensitive than FEV1 alone.
•Dependent on patient understanding and maximal effort.
•Infection control necessary in patients with known or suspected transmissible disease (e.g. active pulmonary TB).
•Assessment of response to therapy.
1.Ask patient to fill in questionnaire.
2.Subject rates on a scale of 0–4 the frequency of 16 different symptoms.
Use the following scale to choose the most appropriate number for each symptom:
0 = Would NEVER experience that symptom
1 = RARELY experience that symptom
2 = SOMETIMES experience that symptom
3 = OFTEN experience that symptom
4 = VERY OFTEN experience that symptom
•Bloated feeling in the stomach.
•Tight feelings around the mouth.
Nijmegen score is the sum of 16 item scores and can range from 0 to 64.
Clinically normal score <23.
•ABGs to identify hypocapnia and respiratory alkalosis.
•Hyperventilation provocation test. (Ask the patient to over-breathe for several minutes to see if it reproduces symptoms.)
Limited by the patient’s ability to read and comprehend the questionnaire and answer questions honestly.
Van Dixhoorn J, Duivenvoorden HJ. Efficacy of Nijmegen Questionnaire in recognition of the hyperventilation syndrome. J Psychosom Res 1985; 29: 199–206.
•Assessment of treatment response to β2-agonists.
Patients need to be equipped with a peak flow meter and a peak flow and symptom diary, and have a thorough understanding of how to use them.
1.Perform the test standing (if possible).
2.Hold the meter lightly and do not interfere with the movement of the marker.
3.Perform three tests each time and record the largest value.
Readings should be taken at various times throughout the day. Limiting the patient to two readings in each day may aid compliance. In occupational asthma, 2-hourly peak flow readings are required during the day and evening.
•Diurnal variability: as measured by the lowest PEFR value (usually on waking) and the highest PEFR value (usually in the afternoon/evening).
•Patient symptoms and PEFR can be examined together.
Diurnal variation is ↑ in patients with asthma, compared with normals (amplitude >20%), i.e. peak flow falls significantly overnight and in the early morning (see Figs 8.4 and 8.5).
•Saves time of the respiratory physician and technician.
•Objective measure of response to treatment.
•Airway hyperresponsiveness test or histamine/methacholine challenge test.
•Sputum cytology: eosinophilia.
•Not all asthma exacerbations are associated with ↑ diurnal variability.
•Calculating diurnal variation can be complicated and tedious.
•Time of recording or recent use of β2-agonist drugs may result in minor changes in peak flow but can cause large errors in diurnal variability.
•Dependent on patient understanding, cooperation, and accuracy.
Hetzel MR, Clark TJ. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate. Thorax 1989; 35: 732–8.
Reddel H, Jenkins C, Woolcock A. Diurnal variability—time to change asthma guidelines? BMJ 1999; 319: 45–7.
•Pleural effusion of unknown aetiology, especially if TB or malignancy suspected.
Note: if malignancy is suspected and areas of pleural nodularity are shown on a contrast-enhanced CT, an image-guided cutting needle is the percutaneous pleural biopsy method of choice.
Abrams’ needle biopsies are only diagnostically useful in areas with a high incidence of TB.
3.Posterior or mid-axillary approach using USS guidance.
4.Skin cleaned with antiseptic solution.
5.Lidocaine (1%) infiltrated in rib interspace. Check pleural fluid aspirated.
6.Stab incision with a narrow scalpel.
7.Insert closed Abrams’ needle (requires firm pressure to be applied until it penetrates the parietal pleura—take care not to apply too much force).
9.Twist open the Abrams’ needle.
10.Aspirate fluid to ensure needle in pleural space.
11.Withdraw needle at angle to chest wall until side hole ‘snags’ parietal pleura.
12.Maintain lateral pressure and rotate to close hole, thereby cutting biopsy. Remove needle and extract biopsy tissue.
13.Repeat with samples taken from 3, 6, and 9 o’clock position (avoid the 12 o’clock position to avoid the neurovascular bundle).
14.May require suture to close.
17.Place samples in formalin for histological examination, and saline for microbiological culture.
•Slivers of white pleural tissue.
•Examine histology and culture for acid- and alcohol-fast bacilli (AAFB).
•Malignant mesothelioma may be diagnosed on histology, especially with addition of immunohistochemical methods looking at tumour cell markers.
•More sensitive than pleural fluid aspiration in diagnosing TB.
•Carcinoma cells may arise from direct spread from lung 1° or represent 2° carcinoma. In either case, management is palliative.
•Easy, quick, cheap; more reliable than diagnostic pleural aspiration.
•Less invasive than thoracoscopy for diagnosis of TB.
•Diagnostic pleural fluid aspiration.
•Image-guided cutting needle pleural biopsy is more sensitive than Abrams’ pleural biopsy at diagnosing malignancy.
•Skeletal muscle biopsy—inadequate specimen.
•Damage to neurovascular bundle.
•Diagnosis of mesothelioma may remain equivocal.
Benamore RE, Scott K, Richards CJ, Entwisle JJ. Image-guided pleural biopsy: diagnostic yield and complications. Clin Radiol 2006; 61: 700–5.
Kirsch CM, Kroe DM, Azzi RL, Jensen WA, Kagawa FT, Wehner JH. The optimal number of pleural biopsy specimens for a diagnosis of tuberculous pleurisy. Chest 1997; 112: 702–6.
Kirsch CM, Kroe DM, Jensen WA, Kagawa FT, Wehner JH, Campagna AC. A modified Abrams needle biopsy technique. Chest 1995; 108: 982–6.
Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361: 1326–30.
Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc 1985; 60: 158–64.
Note: symptoms alone do not help predict which patient with sleep disturbance has OSA.
•Patients with low-probability sleep disorder, e.g. snores with no other features suggestive of OSA.
•Patients with high-probability sleep disorder, e.g. typical symptoms and physiognomy. Need study for diagnosis and assessment of severity.
•Known OSA—assessing treatment response.
•Assessment of nocturnal hypoventilation syndromes, e.g. scoliosis.
•Patients with unexplained sleep–wake disorders.
The patient is admitted to the sleep laboratory in the early evening. Monitoring is explained and attached, using some combination shown in Table 8.5.
Table 8.5 Monitoring combinations
| Sleep | ||
| Oxygenation | O2 saturation probe (ear or finger) | |
| Breathing pattern | ||
| Miscellaneous |
Original diagnosis of OSA based on polysomnography—overnight recording of sleep, breathing patterns, and oxygenation. It is relatively expensive, and most centres use a combination of video to assess the quality of sleep and identify transient arousals and paroxysmal leg movement disorder (PLMD), and oximetry (to detect desaturation), plus some form of measuring the breathing pattern to detect hypopnoea.
OSA diagnosed in the context of multiple (typically >15/h) hypopnoeic/apnoeic events occurring throughout the night and resulting in desaturation.
Demonstrates a number of hypopnoeic (reduction in breathing) or apnoeic (absence of breathing) events occurring per hour. May be used to monitor effectiveness of treatment.
•Most sleep study systems are poorly validated; therefore, need expert interpretation of results to consider false +ves and −ves.
•Patients need to sleep for >3h/night and have rapid eye movement (REM) sleep.
British Thoracic Society (2009). IMPRESS service specification for investigation and treatment of obstructive sleep apnoea syndrome. https://www.brit-thoracic.org.uk/document-library/clinical-information/sleep-apnoea/impress-service-specification-for-investigation-and-treatment-of-osas/.
•Any acutely unwell patient: avoids repeated blood gas measurements, provided that hypercapnia is absent.
•Monitoring of long-term oxygen therapy (LTOT): not suitable for initial assessment.
•Assessment of nocturnal FiO2and screening for sleep apnoea syndrome: identification of nocturnal desaturations.
•Respiratory failure unlikely if SpO2 >92% on air.
•Provides almost immediate arterial O2 saturation data.
•Must know the FiO2 the patient is breathing.
•If COHb or methaemoglobin (MetHb) is present in the blood in elevated levels, the pulse oximeter will give a falsely elevated reading for the arterial O2 saturation.
•Erroneous information if patient poorly perfused.
•Excessive patient movement can give false readings.
•To evaluate atopy in asthmatic individuals.
•To assess the possible development of ABPA in patients with asthma/other long-standing lung disease.
1.Explain what the test involves.
2.Use a pen to label the patient’s forearm with the antigens to be tested, including +ve and −ve controls (alternatively, numbered adhesive tape may be used).
3.Clean the test area with an alcohol wipe.
4.Place a drop of antigen next to each corresponding label.
5.Use a lancet to puncture the skin. Repeat with other antigens using a new lancet each time.
6.Blot off excess antigen, taking care not to contaminate other test sites.
7.After 10min, measure any resulting wheal reactions using a ruler. Record the mean diameter in mm.
A +ve result is indicated by a wheal and flare reaction of 3mm, providing there is no reaction at the −ve control site. −ve results are validated by a wheal reaction at the +ve control site.
A +ve result indicates sensitization to the allergen but does not necessarily mean that this allergen is responsible for the patient’s symptoms. All tests should be carefully interpreted in light of the clinical history.
•Specific IgE to allergens (especially where the history is not supported by skin test results).
•Total IgE (affects interpretation of weak +ve specific IgE results, which are less relevant if the total IgE is very high).
•Aspergillus precipitins (IgG).
•False −ve results if the patient has taken an antihistamine within 5 days of the test.
•False +ve results with dermatographism or inflamed skin.
•To evaluate symptoms, signs, or abnormal test results.
•Provide objective, quantifiable measures of lung function.
•Evaluate and monitor disease.
•Assess effects of environmental/occupational/drug exposures, both adverse (e.g. amiodarone) and beneficial (e.g. bronchodilators).
•Employment/insurance assessment.
•Early detection of bronchiolitis obliterans in lung transplant patients.
1.Explain what the test involves. Most respiratory technicians demonstrate the technique to ensure maximal effort and co-operation of the patient.
2.Patient must inhale fully before the test.
3.Exhale into the breathing tube. Encourage maximal effort with no breath-holding before the manoeuvre.
4.No cough/glottal closure in the first second.
5.Test should last at least 6s (may need up to 15s with obstruction).
(See Table 8.6.)
At least three acceptable tracings should be obtained. Examine each tracing to ensure adequate effort is made by the patient, that it is reproducible, and that there are no artefacts (see Table 8.7).
•Total lung capacity (TLC): to confirm interstitial disease with restrictive spirometry.
•Pre- and post-bronchodilator studies: an ↑ of 15% in FEV1 and 20% in FVC suggest reversibility.
If used for monitoring purposes, need an adequate baseline study.
•Need standardization of normal data for height, weight, age, sex, and race.
•Level at which a result may be considered abnormal is contentious, usually accepted to be outside the range of 80–120% of mean predicted.
•FEV1 may remain relatively normal in early stages of generalized lung disease.
•FEV1/FVC ratio is a good guide to the presence of significant airway narrowing, but as disease progresses, both will fall and correlation with severity of disease is poor.
•Variability (noise) is greater in pulmonary function tests than in most other clinical laboratory tests because of the inconsistency of effort by patients.
For examples of spirograms, see Fig. 8.6 and OHCM 10e, p. 163.
Crapo RO. Pulmonary-function testing. N Engl J Med 1994; 331: 25–30.
•Productive cough with sputum.
•Infective exacerbations of any chronic lung disease.
•Suspected lung cancer: only in elderly/frail patients who are not fit for invasive investigation.
•Sputum eosinophilia in asthma.
•Explain the need for a sputum sample.
•Provide suitable sputum pots.
•Early morning samples are best.
•Consider induced sputum—use ultrasonically nebulized hypertonic saline to facilitate sputum production, in association with chest physiotherapy.
Induced sputum results in successful sputum production in >70% of normal and asthmatic subjects who cannot produce sputum spontaneously (see Table 8.8).
| Gram stain | Gram +ve or −ve organisms |
| ZN stain | AAFB |
| Microscopy | |
| Cytology |
•Streptococcus pneumoniae and Haemophilus influenzae likely pathogens in COPD.
•S. pneumoniae commonest organism in community-acquired 1° pneumonia.
•Staphylococcus aureus and Pseudomonas likely in bronchiectasis.
•The sensitivity of sputum cytology varies by location of the lung cancer and is greatest in central endobronchial lesions.
•Serum serology if atypical pneumonia suspected.
•If bronchiectasis suspected, consider high-resolution CT (HRCT) chest ± CT sinuses, and check Igs (IgG, IgA, and IgM). Other investigations depend on the clinical scenario (RF, IgG subclasses, IgE, Aspergillus IgE and precipitins, α1-antitrypsin). Involve the respiratory team early.
•Sputum may be diluted by saliva.
•Diagnosis of squamous cell carcinoma is not as robust as for small-cell lung cancer or adenocarcinoma. Needs careful cross-referencing to radiology and should be confirmed, if possible, with biopsies.
•−ve results should not preclude further investigations if malignancy suspected.
Pasteur M, Bilton D, Hill A; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65(Suppl 1): i1–58.
Rosia E, Scano G. Association of sputum parameters with clinical and functional measurements in asthma. Thorax 2000; 55: 235–8.
•Differentiate between obstructive and restrictive disease patterns.
•Identify and quantify trapped air (shown by ↑ residual volume (RV)/TLC ratio).
•Assess response to therapeutic interventions (e.g. drugs, radiation, transplantation).
•Identify the presence and amount of unventilated lung.
•Assess chronic lung disease (e.g. sarcoidosis, rheumatoid lung).
•Assessment of pulmonary disability.
1.Ask the patient to wear comfortable clothes.
2.Place the mouthpiece securely in the mouth with the lips tight around it.
3.Breathe in a relaxed manner through the spirometer system (nose clips mandatory).
4.After a total of five tidal breaths with consistent end-expiratory levels, patient asked to maximally inspire to TLC, followed by exhalation with encouragement to force out the last 5–15% of air.
5.A minimum of two attempts should be obtained.
6.More may be needed in the young and elderly to obtain reproducible results.
Most accurate results are obtained with whole body plethysmography.
•Total lung capacity: volume of air in the lungs at the end of full inspiration.
•Residual volume: volume of air remaining in the lungs after maximal expiration.
•Vital capacity: the amount of air expired (or inspired) between maximum inspiration and maximum expiration.
•Functional residual capacity: the amount of air in the lungs at the end-tidal position.
•Inspiratory capacity: the maximum amount of air that can be breathed into the lungs from the end-tidal position.
•Tidal volume: the volume of air inspired and expired with each breath.
•Inspiratory reserve volume: the volume between the peak inspiratory tidal position and maximum inspiration.
•Only interpret if the test is reproducible, i.e. if the two largest VC values are within 5% or 100mL (whichever is the larger).
•VC may remain within normal range in some pulmonary disease, e.g. emphysema.
•↓ VC—restrictive pulmonary disease, neuromuscular disease, e.g. amyotrophic lateral sclerosis.
•During the testing process, the patient is enclosed in a chamber equipped to measure either pressure, flow, or volume changes. Because all the gas in the thorax is accounted for, this method is particularly useful in patients with trapped gas, e.g. bullous emphysema.
•Patient co-operation is essential. They must provide maximal effort and be capable of understanding instructions.
•Calibration should take place on a regular basis.
•Risk of disease transmission between patients, and between patient and technician; therefore, avoid if pulmonary TB suspected.
•Bronchiectasis/recurrent chest infections.
1.Obtain informed consent: verbal usually sufficient, but important to discuss the reasons for the test and possible implications. Perform two sweat tests simultaneously on each arm for greater accuracy.
2.Induce sweating by pilocarpine iontophoresis. A weak electrical current aids penetration of pilocarpine into the skin, thus stimulating the sweat glands of the forearm, previously washed and dried, to secrete sweat.
3.Collect sweat on preweighed filter paper (>100mg), then measure eluted Na+ and chloride (Cl−).
•98–99% of children homozygous for CyF have sweat Cl− and Na+ levels well above 70 and 60mmol/L, respectively.
•Sweat Na+ concentrations tend to ↑ with age and show wide variability between individuals.
•Diagnostic accuracy is improved in borderline cases by a suppression test using fludrocortisone.
•A +ve test is virtually diagnostic of CyF. This should lead to counselling and genetic testing.
•Equivocal results are defined as Na+ or Cl− concentrations between 50 and 70mmol/L.
•The diagnosis should never rest on the sweat test alone and should be considered together with the clinical findings and laboratory evidence of pancreatic insufficiency.
•Assesses functional deficit, therefore capable of detecting patients who have rare variants of CyF.
•Pancreatic function tests (3-day faecal collection).
•A wide discrepancy between the results from each arm suggests a problem with the technique.
•Accurate interpretation of sweat tests requires knowledge of the age-related changes in sweat Na+ and Cl− concentrations and should be done in a specialized centre.
•Poor iontophoretic contact with the skin.
•Evaporation of sweat 2° to inadequate sealing during collection.
•Untreated adrenal insufficiency.
•AIDS (some reports of abnormal sweat electrolytes).
Green A, Dodds P, Pennock C. A study of sweat sodium and chloride: criteria for the diagnosis of cystic fibrosis. Ann Clin Biochem 1985; 22: 171–6.
Hall SK, Stableforth DE, Green A. Sweat sodium and chloride concentrations—essential criteria for the diagnosis of cystic fibrosis in adults. Ann Clin Biochem 1990; 27: 318–20.
Heeley AF, Watson D. Cystic fibrosis—its biochemical detection. Clin Chem 1983; 29: 2011–18.
•Pleural effusions when pleural fluid analysis non-diagnostic.
•Diagnosis of malignant mesothelioma and other pleural abnormalities, e.g. neurinomas, lipomas, plastocytomas.
•A recent (<1 month) CT scan of the chest is mandatory. A pre-procedure USS is desirable.
•Renal function and electrolytes.
•ABGs on air if hypoxaemia suggested by SpO2 or if significant hypercapnia is suspected.
1.Patient informed and consented. Fasted from solids for 6h and liquids for 3h.
4.Patient positioned in the lateral position with the side to be examined uppermost.
5.Basic monitoring: pulse oximeter, BP, and cardiac monitor.
6.Supplementary O2 given via face mask or nasal cannulae to maintain saturations >92%.
7.IV sedation—midazolam/alfentanil. LAn: 0.5–1% lidocaine.
8.An absolute prerequisite for thoracoscopy is the presence of an adequate pleural space (i.e. at least 6–10cm diameter).
9.If pleural effusion: drain using a 3-way tap. Replace with equal quantity of atmospheric air.
10.If no effusion: create a pneumothorax. Insert a needle connected to a manometer into the pleural space. Introduce 400–1000mL of air.
11.Skin incision 1cm in fifth intercostal space, mid-axillary line (or guided by USS).
12.Insert 5–10mm pleural trocar and cannula.
13.Introduce the thoracoscope via the trocar into the pleural cavity.
14.After inspection and biopsies, remove the trocar and insert a drain.
16.May need to apply suction to the drain: ↑ in small increments of 5cmH2O (0.5kPa), up to a maximum of −20cmH2O.
•Direct inspection of pleural surfaces.
•Biopsy of parietal pleura—histology/culture, especially AAFBs.
•Pleural fluid → M,C&S → cytology.
•Therapeutic options: pleurodesis, coagulation of blebs, resection of fibrinous loculations in empyemas.
•Drainage of large pleural effusions possible without risk of re-expansion pulmonary oedema due to rapid equalization of pressures by entrance of air into the pleural space.
•Macroscopic appearance of pleura may be diagnostic, e.g. metastatic disease.
•Better than blind pleural biopsy.
•Able to obtain diagnosis in 70–95% of cases.
•Especially good at diagnosing TB.
•Less invasive than thoracotomy.
•Can perform talc poudrage (pleurodesis) at the same time.
•Less expensive than surgical VATS. Does not require a theatre or an anaesthetist.
•Done under sedation, unlike VATS which requires GAn and selective one-lung ventilation.
•Diagnosis of mesothelioma improved with use of immunohistochemical markers.
•Biopsies may be inadequate or non-representative.
•Patient SOB at rest, unless 2° to pneumothorax or pleural effusion, which can be treated during the procedure.
•Recent MI, arrhythmias, heart failure.
•Bronchopleural fistula following lung biopsy.
•Seeding of metastases/mesothelioma along trocar wound. (Radiotherapy a few weeks post-thoracoscopy should be carried out to prevent this.)
Blanc FX, Atassi K, Bignon J, Housset B. Diagnostic value of medical thoracoscopy in pleural disease: a 6-year retrospective study. Chest 2002; 5: 1677–83.
Buchanan DR, Neville E.Thoracoscopy for physicians: a practical guide. London: Arnold, 2004.
Colt HG. Thoracoscopy: window to the pleural space. Chest 1999; 116: 1409–15.
Loddenkemper R. Thoracoscopy—state of the art. Eur Resp J 1998; 11: 213–21.
•Test for abnormalities of pulmonary gas exchange.
•Avoid smoking 6h prior and strenuous exercise 2h prior.
•Usually measured by single-breath inhalation technique.
•Patient breathes in air containing a known concentration of carbon monoxide (CO) and holds breath for 10s.
•May need to correct for anaemia:
•Result usually standardized to Hb 14.6g/dL.
•Effect of mild anaemia (Hb >10g/dL) slight but becomes progressively more marked at lower values.
•Obstructive lung disease, e.g. COPD, emphysema.
•Diffuse ILD, e.g. cryptogenic fibrosing alveolitis (CFA), amiodarone lung.
•Pulmonary involvement in systemic disease, e.g. SLE, RA, Wegener’s.
•Cardiovascular disease, e.g. pulmonary oedema, mitral stenosis, PE.
•Others: anaemia, cigarette smoking.
•Diseases associated with polycythaemia.
•Diseases associated with ↑ pulmonary blood such as left-to-right intra-cardiac shunts.
•Asthmatics (reasons not clear).
•Breath-holding time may be difficult for some patients to achieve.
•Calculation of TLCO is based on assumption that ventilation and diffusion are homogeneous in the entire lung. With unequal distribution of ventilation and diffusion, the TLCO will be underestimated on the alveolar level.
•With extrapulmonary lung restriction and consequent inability to achieve full inspiration, KCO tends to be higher than normal.
