Investigations in Asthma - Research Paper Example

Investigations in asthma. Asthma is a clinical syndrome of unknown etiology characterized by three distinct components: (1) recurrent episodes of airway obstruction that resolve spontaneously or as a result of treatment; (2) exaggerated bronchoconstrictor response to stimuli that have little or no effect in nonasthmatic subjects, a phenomenon known as airway hyperresponsiveness; and (3) inflammation of the airways.(Drezen 2007). A large national study has revealed that in UK the incidence rate of asthma has decreased in the last few years from 6.9 per 1000 patient years in 2001 to 5.2 per 1000 patient years in 2005. This decrease is most prominent in children under 5 years of age. This group also shows a decrease in the lifetime prevalence of asthma. In adults however, the lifetime prevalence has increased with one person in every nine being diagnosed with asthma.( Simpson & Shiekh 2010). These figures show that asthma is one of the major health problems we face today. The investigations carried out in a case of asthma depend upon the mode of presentation of the patient. My patient presented with acute severe asthma, with a wide spread expiratory wheeze. In such a patient, the initial investigations will be aimed at analyzing rapidly the condition of the patient and determining the emergency measures that need to be instituted. The initial investigation carried out in almost all patients presenting with asthma is the measurement of the peak expiratory flow rate( PEFR). The pulmonary function tests are significant tools in the diagnosis of asthma. Measurement of peak expiratory flow rate and spirometry are the two pulmonary function tests most often used in the diagnosis of asthma. PEF gives an idea of the severity of the asthma. The normal value of PEFR varies with age, sex, height and race, but in general, the range is 500-700 L/min for men and 380-500 L/min for women.(Marino & Sutin 2007). For the purpose of assessment of asthma severity, PEFR of the patient is considered as a percentage of the predicted PEFR. If the PEFR is between 75 to 100% of the predicted value, then the asthma is mild. With values between 50 and 75 percent of expected value, the asthma is classified as moderate, while a value of less than 50 % of the expected value or a PEFR of less than 200L/min would be classified as severe asthma(Boon, Colledge, Walker & Hunter 2006), requiring iv steroids and nebulized salbutamol and terbutaline. Because PEF meters are inexpensive and widely available, they also play an important role in confirmation of a diagnosis of asthma in patients with mild symptoms. The patients are told to record morning and evening values of PEF. Morning values 20 % lower than evening values are indicative of asthma, as is improvement in symptoms after administration of corticosteroids for a period of 3 weeks. (Boon, Colledge, Walker & Hunter 2006.) Studies demonstrate that PEF meters are a patient friendly method of monitoring of disease progression although prolonged periods of measurement are met with decreased patient compliance. Compliance with PEF measurements was found to be good during the first month (63% of the measurements done) but even with regular reinforcement, fell to 50% at 6 months and to 33% at 12 months. (Cote, Cartier and Malo 1998). Furthermore it has been found that individualized action plans based on the patients best PEFR measurements consistently improve asthma health outcomes. (Gibson & Powell 2004). PEFR measurements are also useful in the diagnosis of occupational asthma. If PEFR measurements are made every 2 hours over a period of 2 weeks, including a period of time away from work then the sensitivity and specificity of this test for the detection of occupational asthma are 71 and 84% respectively(Perrin & Lagier 1992). PEFR measurement is useful however it also has certain shortcomings which may influence the investigation. Some degree of airflow obstruction may be present when the peak flow remains within the normal range. Peak flow measurements are not enough to distinguish upper airway obstruction from asthma. Reduced peak flow measurements may be seen in both obstructive and restrictive diseases. Errors in performing the test frequently lead to underestimation of true values, and occasionally to overestimation as they are also based on patient technique. Finally peak flow meters cannot be routinely calibrated (Enright 1994). In my patient, the next few relevant investigations to be carried out in the ER would be focused on the emergency management: Arterial blood gases to assess the level of the respiratory compromise. ABG analysis does not need to be undertaken in patients with mild to moderate asthma. In severe prolonged asthma, hypoxemia and hypocapnia are the rule. PaO2 is usually between 55 and 75 mm Hg and PCO2 is between 25 and 35 mm Hg. At the onset of the attack, an appropriate pure respiratory alkalemia is usually evident; with attacks of prolonged duration, the pH normalizes as a result of a compensatory metabolic acidemia. A normal Paco2 in a patient with moderate to severe airflow obstruction is reason for concern because it may indicate that the mechanical load on the respiratory system is greater than can be sustained by the ventilatory muscles and that respiratory failure is imminent. When the Paco2 increases in such settings, the pH decreases quickly because the bicarbonate stores have become depleted as a result of renal compensation for the prolonged preceding respiratory alkalemia. Because this chain of events can take place rapidly, close observation is indicated for asthmatic patients with “normal” Paco2 levels and moderate to severe airflow obstruction. (Drezen 2007). In the initial assessment of acute severe asthma an oxygen saturation of > 92% suggests that respiratory failure is unlikely and therefore arterial blood gas measurement is unnecessary.(Carruthers and Harrison 1995) Plasma theophylline levels so that if i.v aminophylline is to be given, concerns about toxicity or exceeding serum therapeutic levels would not be an impediment to treatment. Plasma potassium levels because salbutamol nebulization would cause movement of potassium into cells and if the levels are already low, the condition of an already compromised patient could be further worsened. In a stable patient presenting with asthmic symptoms the next investigation would be spirometry. The two main investigations utilized are FEV1 and FVC. FEV1 is the volume of air that can be forcibly expired in the first second of a forced expiratory manouvere(Booker 2006) and the FVC is the volume of gas that can be expired as forcefully and rapidly as possible after maximal inspiration(Barash & Cullen 2009). A ratio of FEV1/ FVC less than 80% of expected is indicative of airflow obstruction and an improvement of 15%(or 200ml) after administration of a bronchodilator is diagnostic of asthma( Booker 2006). Acute reversibility of airflow obstruction is tested by administering two to four puffs of a quick-acting bronchodilator such as albuterol and repeating the spirometry 15 minutes later. The ability of spirometry to differentiate between asthma and COPD has been called into question because acute responses of FEV1 and FVC following a standard dose of inhaled bronchodilator are neither sufficiently sensitive nor sufficiently specific to differentiate asthma from COPD purely on spirometric grounds(Kesten & Rebuck 1994). The variability of the measurement is such that an increase of less than 12 percent may occur simply due to making repeated measurements. An increase in FEV1 of 12 percent or more, accompanied by an absolute increase in FEV1 of at least 200 mL, can be attributed to bronchodilator responsiveness with 95 percent certainty (Enright 1994). If the patient presents with normal flow rates, different stimuli that could possibly induce bronchoconstriction can be tried to induce airway hyper-responsiveness, especially to determine the inciting agent in occupational asthma. “Bronchoprovocative testing can be thought of as being similar to exercise stress testing in a patient suspected of having angina who has a normal resting electrocardiogram” (Fanta, Fletcher 2009). The stimulus used to investigate for asthma is inhaled methacholine, although exercise, cold air, or inhaled histamine are potential alternatives (Pratter 1989). Studies have however shown that laboratory testing results may underestimate the actual effects of these agents on the airways. (Malo & Cartier 2003). A variety of direct and indirect stimuli including exercise, cold air, dusts, smoke and chemicals such as histamine and methacholine may be helpful in patients presenting with normal lung function. AHR is sensitive but non-specific: it therefore has a high negative predictive value but positive results may be seen in other conditions such as COPD, bronchiectasis and CF. Challenge tests using adenosine are being developed and may prove more specific. . (Boon, Colledge, Walker & Hunter 2006.) The role of chest x rays in the diagnosis of asthma is mainly in the exclusion of other alternate diagnoses which mimic asthma like allergic bronchopulmonary aspergillosis and bronchiectasis or to assess the presence of complications. Eggleston. Pearman and Bierson tracked 515 asthma admissions of which 479 had admission chest films, 22.3% of which were abnormal. Significant perihilar infiltrates were the most frequent abnormality seen; atelectasis, especially of the right middle lobe, was the next most frequent. Pneumomediastinum was also a common finding. Both pneumomediastinum and infiltrates were strikingly age-dependent: 15.5% over 10 years old had pneumomediastinum; none under 2 years old had this complication;infiltrates occurred in nearly 25% of younger children but in only 8.3% over 10 years old. Since pulmonary complications substantially alter therapeutic management, a chest x ray should be part of the initial evaluation of any child hospitalized with acute asthma. (1974). Because of the strong correlation between asthma and atopy, allergy should be ruled out as a cause of the asthma. The investigations that are used are: Plasma eosinophil count Skin prick tests Serum total IgE Allergen specific IgE(Boon, Colledge, Walker & Hunter 2006.) History taking is the first step in determining allergic sensitivity. Allergens such as house dust mite antigen, pollens, danders from dogs and cats, and mold spores are found to be main causes for asthma. Measurement of serum total immunoglobulin E (IgE) indicate the presence of underlying allergic disease. A very high total IgE level (>1000 IU/mL) suggests the associated conditions of eczema or allergic bronchopulmonary aspergillosis (Fanta, Fletcher 2009). Allergic sensitivity to specific are assesses by two specific modalities; allergy skin tests and blood tests for allergen-specific IgE. The in vitro blood tests for allergen-specific IgE most commonly utilize fluorescence-based immunoassays. These tests have largely replaced radioallergosorbent tests (RAST) tests and measure minute quantities of IgE antibody specifically directed at particular antigens (as opposed to the total serum IgE discussed above). Various panels of antibodies can be ordered. The main advantage of in vitro testing over skin testing is the risk of adverse reactions decreases. The disadvantages include a higher cost and decreased sensitivity as compared with skin testing (Malo, Lemiere 2009). In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed TH1 and TH2, the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown. As compared with the control subjects, the subjects with asthma had more BAL cells per 1000 cell that were positive for mRNA for interleukin-2, 3, 4, and 5 and GM-CSF. There was no significant difference between the two groups in the number of cells expressing mRNA for interferon gamma. In the subjects with asthma, mRNA for interleukin-4 and 5 was expressed predominantly by T lymphocytes.(Robinson and Hamid 1992). The fraction of NO• in the exhaled air (FENO) is elevated in patients with asthma. Although the exact concentration considered “elevated” will vary with the details of the technique, a concentration of 15 parts per billion is a convenient and reliable level that can be used to distinguish normal subjects from patients with untreated asthma. Because inhaled steroids suppress Feno levels, these values can guide titration of the dose of inhaled corticosteroids and are better than use of symptoms for this purpose(Drezen 2007). The utility of measurements of exhaled nitric oxide will likely depend on context, being most helpful in moderate and severe asthma, rather than mild asthmatics and community based studies. Atopy on its own is a cause of elevation in FeNO. The relationship between FeNO and sputum eosinophils is relatively loose, but this does not preclude it being a useful test in clinical practice. A low FeNO in the setting of supposedly poorly controlled asthma should cast doubt on the diagnosis. If FeNO is elevated, particularly if asthma is uncontrolled, it suggests an imbalance between anti-inflammatory therapy and pro-inflammatory environmental influences. Inadequate anti-inflammatory therapy may be due to the prescribed dose being too low; the drug delivery device not being used correctly; or the medication not being taken. Adverse pro-inflammatory environmental influences driving up FeNO include IgE and non-IgE mediated allergen sensitivity in the home, and even in the child's school.(Bush & Eber 2008). The different investigative modalities available for the diagnosis of asthma have two key fundamentals. These are the history or presence of respiratory symptoms consistent with asthma, and the demonstration of variable expiratory airflow obstruction. The 2007 asthma guidelines of the National Asthma Education and Prevention Program (NAEPP) recommend that spirometry, before and after administration of a bronchodilator, be performed in all adolescents and adults that are presenting with the symptoms of asthma (NAEPP 2007). Spirometry and bronchoprovocation testing help demonstrate reversible airflow obstruction and it is particularly important when the patient is not responding to therapy. Pulmonary function testing also helps to limit under diagnosis of asthma. In patients presenting in an emergency department, the diagnosis is made when asthmatic symptoms resolve over the course of minutes to hours in response to bronchodilators and glucocorticoids (Irvin, Curley, French 1990). The British Thoracic Society guidelines for the management of children with asthma divide patients on the basis of assessment of clinical symptoms into three categories: in those with a high probability of asthma(wheeze, cough, chest tightness, positive personal or family history), it is recommended that a trial of treatment is given, response is reviewed and further investigation is reserved for those with a poor response. In those with an intermediate probability(diagnosis uncertain), perform spirometry for evidence of airway obstruction and assess post bronchodilator FEV1 and PEF. If there is no evidence of airway obstruction, consider testing for atopic status, bronchodilator reversibility and if possible bronchial hyperresponsivness using exercise, methacholine or histamine. In children with low probability of asthma consider referral to a specialist and more detailed investigation. (British Thoracic Organization Guidelines). References 1. British Thoracic Society. “2008 British Guidelines for the Diagnosis of Asthma.” 2. Boon, Nicholas. Colledge, Nicki. Walker, Brian. Hunter, John. 2006. “Davidsons Principles and Practice of Medicine.” 20 edition. 3. Booker, Rachel. 2006. “Vital lung function.” Pg 61. 4. Bush, A. Eber, E. 2008. “The value of FeNO measurement in asthma management.” Pediatric Respiratory Review. Pg 127. 5. Cote, Johanne. Cartier, Andre. Malo, Jean Luc. 1998. “Compliance With Peak Expiratory Flow Monitoring in Home Management of Asthma.” CHEST. Vol 113. 6. Caruthers, D. Harrison, B. 1995. “Arterial blood gas analysis or oxygen saturation in the assessment of acute asthma?” THORAX. Volume 50. 7. Drezen, Jeffrey. 2007. “Cecil Medicine.” 23 edition. Chapter 87. 8. Eggleston, Peytom. Bierman, Warren. Pearson, William. 1994. “Radiographic Abnormalitie in acute asthma in Children.” Official Journal of the American Academy of Pediatrics. Volume 54. 9. Enright, P. Lebowitz, M. Cockcroft, D. 1994. “ Physiologic measures: Pulmonary function test.” Am J Respiratory Critical Care Medical volume 149. 10. Fanta, Christopher. Fletcher, Suzanne. 2009. “Diagnosis of asthma in adolescents and adults” UpToDate Review. 11. Gibson, P. Powell, H. 2004. “Written action plans for asthma: an evidence-based review of the key components.” THORAX. Volume 59. 12. Irwin, R. Curley, F. French, C. 1990. “ Chronic cough: The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.” Am Rev Respir Dis volume 141 13. Kesten, S. Rebuck, A. 1994. “Is the short-term response to inhaled beta-adrenergic agonist sensitive or specific for distinguishing between asthma and COPD?” CHEST. Volume 105. 14. Lagier, F. Perrin, B. 1992. “Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge.” Europeon Respiratory Journal. Volume 5. 15. Marino, Paul. Sutin, Kenneth. 2007. “ The ICU Book.” Pg 438. 16. Malo, J. Cartier, A. 2003. “Exaggerated bronchoconstriction due to inhalation challenges with occupational agents.” Europeon Respiratory Journal. Volume 23. 17. Pratter, MR, Curley, FJ, Dubois, J, Irwin, RS. Cause and evaluation of chronic dyspnea in a pulmonary disease clinic. Arch Intern Med 1989; volume 149. 18. Robinson, D. Hamid, Q. 1992. “Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.” The New England Jornal of Medicine. Volume 326. 19. Simpson, Colin. Shiekh, Aziz. 2010. “Trends in the epidemiology of asthma in England: a national study of 333,294 patients.” Journal of the Royal Society of Medicine. Vol 103. pg 98. 20. National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051). Full text available online: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed September 1, 2007). 21. 22. Malo, Jean-Luc. Lemiere, Catherine. 2009. “Diagnosis and clinical assessment of occupational asthma” UpToDate Review. Read More