Tiêu đề All respiratory Disease .pdf ✅

Obstructive pulmonary diseases • 567 17 irradiation are employed to treat obliterative bronchiolitis but late organ failure remains a significant problem. The major factor limiting the availability of lung transplantation is the shortage of donor lungs. To improve organ availability, techniques to recondition the lungs in vitro after removal from the donor are being developed. Obstructive pulmonary diseases Asthma Asthma is a chronic inflammatory disorder of the airways, in which many cells and cellular elements play a role. Chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night and in the early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible, either spontaneously or with treatment. The prevalence of asthma increased steadily over the latter part of last century. As asthma affects all age groups, it is one of the most common and important long-term respiratory conditions in terms of global years lived with disability (Fig. 17.16). The development and course of asthma and the response to treatment are influenced by genetic determinants, while the rapid rise in prevalence implies that environmental factors are critically important in the development and expression of the disease. The potential role of indoor and outdoor allergens, microbial exposure, diet, vitamins, breastfeeding, tobacco smoke, air pollution and obesity have been explored but no clear consensus has emerged. capacity and quality of life. The various types of non-invasive (via a face or nasal mask) or invasive (via an endotracheal tube) ventilation are detailed on page 202. Respiratory stimulant drugs, such as doxapram, have been superseded by intubation and mechanical ventilation in patients with CO2 narcosis. Home ventilation for chronic respiratory failure NIV is of great value in the long-term treatment of respiratory failure due to spinal deformity, neuromuscular disease and central alveolar hypoventilation. Some patients with advanced lung disease, e.g. cystic fibrosis, also benefit from NIV for respiratory failure. In these conditions, type II respiratory failure can develop slowly and insidiously. Morning headache (due to elevated PaCO2) and fatigue are common symptoms but, in many cases, the diagnosis is revealed only by sleep studies or morning blood gas analysis. In the initial stages, ventilation is insufficient for metabolic needs only during sleep, when there is a physiological decline in ventilatory drive. Over time, however, CO2 retention becomes chronic, with renal compensation of acidosis. Treatment by home-based NIV overnight is often sufficient to restore the daytime PCO2 to normal, and to relieve fatigue and headache. In advanced disease (e.g. muscular dystrophies or cystic fibrosis), daytime NIV may also be required. Lung transplantation Lung transplantation is an established treatment for carefully selected patients with advanced lung disease unresponsive to medical treatment (Box 17.18). Single-lung transplantation may be used for selected patients with advanced emphysema or lung fibrosis. This is contraindicated in patients with chronic bilateral pulmonary infection, such as cystic fibrosis and bronchiectasis, because the transplanted lung is vulnerable to cross-infection in the context of post-transplant immunosuppression, and for these individuals bilateral lung transplantation is the standard procedure. Combined heart–lung transplantation is still occasionally needed for patients with advanced congenital heart disease, such as Eisenmenger’s syndrome, and is preferred by some surgeons for the treatment of primary pulmonary hypertension unresponsive to medical therapy. The prognosis following lung transplantation is improving steadily with modern immunosuppressive drugs: over 50% 10-year survival in some UK centres. Chronic rejection with obliterative bronchiolitis continues to afflict some recipients, however. Glucocorticoids are used to manage acute rejection, but drugs that inhibit cell-mediated immunity specifically, such as ciclosporin, mycophenolate and tacrolimus (p. 89), are used to prevent chronic rejection. Azithromycin, statins and total lymphoid 17.18 Indications for lung transplantation Parenchymal lung disease • Cystic fibrosis • Emphysema • Pulmonary fibrosis • Obliterative bronchiolitis • Langerhans cell histiocytosis (p. 613) • Lymphangioleiomyomatosis (p. 613) Pulmonary vascular disease • Primary pulmonary hypertension • Thromboembolic pulmonary hypertension • Veno-occlusive disease • Eisenmenger’s syndrome (p. 532) Fig. 17.16 The burden of asthma, measured by disability life years (DALYs) per 100 000 population. The burden of asthma is greatest in children approaching adolescence and the elderly. The burden is similar in males and females at ages below 30–34 but at older ages the burden is higher in males. From The Global Asthma Report 2014. Copyright 2014 The Global Asthma Network. 80+ 70–74 75–79 65–69 60–64 55–59 50–54 45–49 40–44 35–39 30–34 25–29 20–24 15–19 10–14 5–9 1–4 DALYs (per 100 000) 0 200 400 600 800 1000 Females Males Years
568 • RESPIRATORY MEDICINE With increasing severity and chronicity of the disease, remodelling of the airway may occur, leading to fibrosis of the airway wall, fixed narrowing of the airway and a reduced response to bronchodilator medication. Clinical features Typical symptoms include recurrent episodes of wheezing, chest tightness, breathlessness and cough. Asthma is commonly mistaken for a cold or a persistent chest infection (e.g. longer than 10 days). Classical precipitants include exercise, particularly in cold weather, exposure to airborne allergens or pollutants, and viral upper respiratory tract infections. Wheeze apart, there is often very little to find on examination. An inspection for nasal polyps and eczema should be performed. Rarely, a vasculitic rash may suggest eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome; p. 1043). Patients with mild intermittent asthma are usually asymptomatic between exacerbations. Individuals with persistent asthma report ongoing breathlessness and wheeze but these are variable, with symptoms fluctuating over the course of one day, or from day to day or month to month. Asthma characteristically displays a diurnal pattern, with symptoms and lung function being worse in the early morning. Particularly when poorly controlled, symptoms such as cough and wheeze disturb sleep. Cough may be the dominant symptom in some patients, and the lack of wheeze or breathlessness may lead to a delay in reaching the diagnosis of so-called ‘cough-variant asthma’. Some patients with asthma have a similar inflammatory response in the upper airway. Careful enquiry should be made as to a history of sinusitis, sinus headache, a blocked or runny nose and loss of sense of smell. Although the aetiology of asthma is often elusive, an attempt should be made to identify any agents that may contribute to the appearance or aggravation of the condition. Particular enquiry should be made about potential allergens, such as exposure to a pet cat, guinea pig, rabbit or horse, pest infestation, exposure to moulds following water damage to a home or building, and any potential occupational agents (p. 613). In some circumstances, the appearance of asthma is triggered by medications. Beta-blockers, even when administered topically Pathophysiology Airway hyper-reactivity (AHR) – the tendency for airways to narrow excessively in response to triggers that have little or no effect in normal individuals – is integral to the diagnosis of asthma and appears to be related, although not exclusively, to airway inflammation (Fig. 17.17). Other factors likely to be important in the behaviour of airway smooth muscle include the degree of airway narrowing and neurogenic mechanisms. The relationship between atopy (the propensity to produce IgE) and asthma is well established and in many individuals there is a clear relationship between sensitisation and allergen exposure, as demonstrated by skin-prick reactivity or elevated serum-specific IgE. Common examples of allergens include house dust mites, pets such as cats and dogs, pests such as cockroaches, and fungi. Inhalation of an allergen into the airway is followed by an early and late-phase bronchoconstrictor response (Fig. 17.18). Allergic mechanisms are also implicated in some cases of occupational asthma (p. 613). In cases of aspirin-sensitive asthma, the ingestion of salicylates results in inhibition of the cyclo-oxygenase enzymes, preferentially shunting the metabolism of arachidonic acid through the lipoxygenase pathway with resultant production of the asthmogenic cysteinyl leukotrienes. In exercise-induced asthma, hyperventilation results in water loss from the pericellular lining fluid of the respiratory mucosa, which, in turn, triggers mediator release. Heat loss from the respiratory mucosa may also be important. In persistent asthma, a chronic and complex inflammatory response ensues, characterised by an influx of numerous inflammatory cells, the transformation and participation of airway structural cells, and the secretion of an array of cytokines, chemokines and growth factors. Examination of the inflammatory cell profile in induced sputum samples demonstrates that, although asthma is predominantly characterised by airway eosinophilia, neutrophilic inflammation predominates in some patients while in others scant inflammation is observed: so-called ‘pauci- granulocytic’ asthma. Fig. 17.17 Airway hyper-reactivity in asthma. This is demonstrated by bronchial challenge tests with sequentially increasing concentrations of either histamine, or methacholine or mannitol. The reactivity of the airways is expressed as the concentration or dose of either chemical required to produce a specific decrease (usually 20%) in the forced expired volume in 1 second (FEV1) (PC20 or PD20, respectively). 40 30 20 10 0 Reduction in FEV1 (%) Increasing concentration of histamine Severe asthma Moderate asthma Mild asthma Normal Fig. 17.18 Changes in peak flow following allergen challenge. A similar biphasic response is observed following a variety of different challenges. Occasionally, an isolated late response is seen with no early reaction. Time (hours) Peak flow (L/min) 400 Early reaction (type I) Pre-formed mediator release Late reaction (type Il) Inflammatory cell recruitment and activation 300 200 100 0 500 0 1 2 3 4 5 6 7 8 24 Challenge, e.g. allergen
Obstructive pulmonary diseases • 569 17 available, a peak flow meter may be used. Symptomatic patients should be instructed to record peak flow readings after rising in the morning and before retiring in the evening. A diurnal variation in PEF of more than 20% (the lowest values typically being recorded in the morning) is considered diagnostic, and the magnitude of variability provides some indication of disease severity (Fig. 17.20). A trial of glucocorticoids (e.g. 30 mg daily for 2 weeks) may be useful in establishing the diagnosis, by demonstrating an improvement in either FEV1 or PEF. It is not uncommon for patients whose symptoms are suggestive of asthma to have normal lung function. In these circumstances, the demonstration of AHR by challenge tests may be useful to confirm the diagnosis (see Fig. 17.17). AHR has a high negative predictive value but positive results may be seen in other conditions, such as COPD, bronchiectasis and cystic fibrosis. The use of exercise tests is useful when symptoms are predominantly related to exercise (Fig. 17.21). The diagnosis may be supported by the presence of atopy demonstrated by skin-prick tests or measurement of total and allergen-specific IgE, an FENO (a surrogate of eosinophilic airway inflammation) of ≥ 40 parts per billion in a glucocorticoid-naïve adult, or a peripheral blood eosinophilia. Chest X-ray appearances are often normal but lobar collapse may be seen if mucus occludes a large bronchus and, if accompanied by the presence of flitting infiltrates, may suggest that asthma has been complicated by allergic bronchopulmonary aspergillosis (p. 596). A high-resolution CT scan (HRCT) may be useful to detect bronchiectasis. Management Setting goals Asthma is a chronic condition but may be controlled with appropriate treatment in the majority of patients. The goal of treatment should be to obtain and maintain complete control (Box 17.20) but aims may be modified according to the circumstances as eye drops, may induce bronchospasm, as may aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). The classical aspirin-sensitive patient is female and presents in middle age with asthma, rhinosinusitis and nasal polyps. Aspirin-sensitive patients may also report symptoms following alcohol and foods containing salicylates. Other medications implicated include the oral contraceptive pill, cholinergic agents and prostaglandin F2α. Betel nuts contain arecoline, which is structurally similar to methacholine and can aggravate asthma. An important minority of patients develop a particularly severe form of asthma and this appears to be more common in women. Allergic triggers are less important and airway neutrophilia predominates. Diagnosis The diagnosis of asthma is predominantly clinical and is based on the combination of the history, lung function and ‘other’ tests, which allows high, intermediate or low probability of asthma to emerge. The approach may vary from patient to patient and may need to be re-evaluated following the introduction of treatment. Supportive evidence is provided by the demonstration of variable airflow obstruction, preferably by using spirometry (Box 17.19) to measure FEV1 and FVC. This identifies the obstructive defect, defines its severity, and provides a baseline for bronchodilator reversibility (Fig. 17.19). If spirometry is not 17.19 How to make a diagnosis of asthma Compatible clinical history plus either/or: • FEV1 ≥ 12% (and 200 mL) increase following administration of a bronchodilator/trial of glucocorticoids. Greater confidence is gained if the increase is > 15% and > 400 mL • > 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary • FEV1 ≥ 15% decrease after 6 mins of exercise (FEV1 = forced expiratory volume in 1 sec; PEF = peak expiratory flow) Fig. 17.19 Reversibility test. Forced expiratory manœuvres before and 20 minutes after inhalation of a β2-adrenoceptor agonist. Note the increase in forced expiratory volume in 1 second (FEV1) from 1.0 to 2.5 L. 7 Time (seconds) 0 5 1 2 3 4 6 Volume expired (L) FEV1 FEV1 20 mins after bronchodilator drug administered 2.5 1 8 Before bronchodilator drug administered Fig. 17.20 Serial recordings of peak expiratory flow (PEF) in a patient with asthma. Note the sharp overnight fall (morning dip) and subsequent rise during the day. Following the introduction of glucocorticoids, there is an improvement in PEF rate and reduction of morning dipping. 500 am am Peak flow (L/min) 300 200 100 pm pm am am pm pm am am pm 1 2 34 5 Time (days) 400 Glucocorticoids commenced
570 • RESPIRATORY MEDICINE pet, may effect improvement. House dust mite exposure may be minimised by replacing carpets with floorboards and using mite- impermeable bedding. So far, improvements in asthma control following such measures have been difficult to demonstrate. Many patients are sensitised to several ubiquitous aeroallergens, making avoidance strategies largely impractical. Measures to reduce fungal exposure may be applicable in specific circumstances and medications known to precipitate or aggravate asthma should be avoided. Smoking cessation (p. 94) is particularly important, as smoking not only encourages sensitisation but also induces a relative glucocorticoid resistance in the airway. The stepwise approach to the management of asthma See Figure 17.22. Step 1: Occasional use of inhaled short-acting β2-adrenoreceptor agonist bronchodilators A variety of different inhaled devices are available and the choice of device should be guided by patient preference and competence Fig. 17.21 Exercise-induced asthma. Serial recordings of forced expiratory volume in 1 second (FEV1) in a patient with bronchial asthma before and after 6 minutes of strenuous exercise. Note initial rise on completion of exercise, followed by sudden fall and gradual recovery. Adequate warm-up exercise or pre-treatment with a β2-adrenoceptor agonist, nedocromil sodium or a leukotriene antagonist can protect against exercise-induced symptoms. 3.5 Time (minutes) 0 25 5 10 15 20 30 FEV1 (L) 3.0 2.5 2.0 Exercise and the patient. Unfortunately, surveys consistently demonstrate that the majority of individuals with asthma report suboptimal control, perhaps reflecting the poor expectations of patients and their clinicians. Whenever possible, patients should be encouraged to take responsibility for managing their own disease. A full explanation of the nature of the condition, the relationship between symptoms and inflammation, the importance of key symptoms such as nocturnal waking, the different types of medication and, if appropriate, the use of PEF to guide management decisions should be given. A variety of tools/questionnaires have been validated to assist in assessing asthma control. Written action plans can be helpful in developing self-management skills. Avoidance of aggravating factors This is particularly important in the management of occupational asthma (p. 613) but may also be relevant in atopic patients, when removing or reducing exposure to relevant antigens, such as a 17.21 Asthma in pregnancy • Clinical course: women with well-controlled asthma usually have good pregnancy outcomes. Pregnancy in women with more severe asthma can precipitate worsening control and lead to increased maternal and neonatal morbidity. • Labour and delivery: 90% have no symptoms. • Safety data: good for β2-agonists, inhaled glucocorticoids, theophyllines, oral prednisolone, and chromones. • Oral leukotriene receptor antagonists: no evidence that these harm the fetus and they should not be stopped in women who have previously demonstrated significant improvement in asthma control prior to pregnancy. • Glucocorticoids: women on maintenance prednisolone > 7.5 mg/ day should receive hydrocortisone 100 mg 3–4 times daily during labour. • Prostaglandin F2α: may induce bronchospasm and should be used with extreme caution. • Breastfeeding: use medications as normal. • Uncontrolled asthma: associated with maternal (hyperemesis, hypertension, pre-eclampsia, vaginal haemorrhage, complicated labour) and fetal (intrauterine growth restriction and low birth weight, preterm birth, increased perinatal mortality, neonatal hypoxia) complications. Characteristic Controlled Partly controlled (any present in any week) Uncontrolled Daytime symptoms None (≤ twice/week) > twice/week ≥ 3 features of partly controlled asthma present in any week Limitations of activities None Any Nocturnal symptoms/awakening None Any Need for rescue/‘reliever’ treatment None (≤ twice/week) > twice/week Lung function (PEF or FEV1) Normal < 80% predicted or personal best (if known) on any day Exacerbation None ≥ 1/year 1 in any week (FEV1 = forced expiratory volume in 1 sec; PEF = peak expiratory flow) } 17.20 Levels of asthma control