AFP Journal Review October 15, 2011

1. AFP Journal ReviewOctober 15, 2011 Lianne Beck, MD Assistant Professor Emory Family Medicine

2. Articles • Evaluation of the Patient with Chronic Cough • Evaluation of Suspected Dementia • Diagnosis of Heel Pain • Premenstrual Syndrome and Premenstrual Dysphoric Disorder

3. Evaluation of the Patient with Chronic Cough • Pathophysiology • Defensive reflex mechanism • Cough center in the medulla receives signals from activated cough receptors via afferent fibers in the vagus nerve • Voluntary inhibition or production of cough due to higher cortical centers • Efferent signals are then sent to the muscles that produce the forced expiratory effort

4. Definition and DDx • Acute (3 weeks) - viral URI, HF, COPD or asthma exacerbation, occupational or environmental exposure to irritants • Subacute (3-8 weeks) - postinfectious secondary to asthma or bacterial sinusitis. • Chronic (> 8 weeks) – UACS (postnasal drip syndrome), asthma, or GERD, alone or in combination

5. Chronic Cough • Two or more causes in 18 to 62 % of patients, and three causes in up to 42 % of patients. • Empiric treatment should be initiated sequentially for the three most common causes of chronic cough until symptoms are resolved. • Patients may need to be treated for multiple causes simultaneously • Treatments should be added to the primary regimen rather than replacing it.

6. UPPER AIRWAY COUGH SYNDROME • Most common cause of chronic cough in nonsmoking, immunocompetent adults who have normal CXR. • Diagnosis based on findings from the history and PE • Drainage in the posterior pharynx, throat clearing, nasal discharge, cobblestone appearance of the oropharyngeal mucosa, and mucus in the oropharynx are relatively sensitive findings but are nonspecific for UACS. • “Silent” UACS

7. Differential Diagnosis of UACS • Allergic fungal sinusitis • Allergic rhinitis • Bacterial sinusitis • Occupational rhinitis • Post-infectious rhinitis • Rhinitis caused by anatomic abnormalities • Rhinitis caused by chemical or physical irritants • Rhinitis medicamentosa • Rhinitis of pregnancy

8. UACS Cont… • A diagnosis can also be made after a trial of therapy. • UACS that is not caused by sinusitis usually responds to a combination of a decongestant and first-generation histamine H1 receptor antagonist. • The nonsedating antihistamines are not as effective if the postnasal drip is not mediated by histamine (e.g., in nonallergic rhinitis). • Sinus imaging if no response • Radiography is 84 % SN and 77 % SP. • Plain radiography used as a screening modality. • CT used to confirm and stage chronic inflammatory diseases of sinonasal cavities.

9. Asthma • Next most common cause of chronic cough in adults • Spirometry is required to diagnose asthma and can be reliably used to demonstrate airflow obstruction and assess reversibility of the condition in patients older than four years. • Cough is the most commonly reported symptom in patients with chronic asthma, and it is the only manifestation in up to 57 % (i.e., cough-variant asthma). • Should be considered when persistent cough is exacerbated by cold or exercise, or is worse at night. • In patients suspected of having cough-variant asthma but who have nondiagnostic physical examination and spirometry, methacholine inhalation challenge testing may be performed to confirm asthma. • Trial of inhaled bronchodilators or corticosteroids is an alternative for diagnosis.

10. GERD (and LPR) • Third leading cause of chronic cough in adults. • Stimulates the afferent limb of the cough reflex by irritating the upper respiratory tract without aspiration or by irritating the lower respiratory tract through aspiration. • Can also cause chronic cough by stimulating an esophageal-bronchial cough reflex. • Through this neural reflex mechanism, refluxate into the distal esophagus alone is thought to be sufficient stimulus to cause cough. • Daily heartburn and regurgitation suggest a GERD-induced chronic cough. • These symptoms may be absent in “silent” GERD.

11. GERD • Although GERD treatment is not universally beneficial for cough associated with the disease, an empiric trial of a PPI is recommended. • Definitive diagnosis of GERD-related cough requires that the cough nearly or completely disappears with treatment. • The most sensitive and specific test for acid-induced GERD is 24-hour esophageal pH monitoring • May be performed if therapeutic trials are ineffective.

12. ACE INHIBITORS • Cause a nonproductive cough in 5 to 20 % of patients, affecting women more often than men. • Is not dose related, and the cough may begin one week to six months after therapy is initiated. • The cough should spontaneously resolve a few days to several weeks after the ACE inhibitor is discontinued • A four-week trial of withdrawal is usually sufficient to determine whether the medication caused the cough. • ARB may be substituted.

13. Nonasthmatic Eosinophilic Bronchitis • Normal airway hyperresponsiveness, sputum eosinophilia, and no symptoms or objective evidence of variable airflow obstruction. • The presence and activation of eosinophils and metachromatic cells in the sputum differentiate nonasthmatic eosinophilic bronchitis from classic chronic bronchitis. • Lack of bronchial hyperresponsiveness in nonasthmatic eosinophilic bronchitis differentiates it from asthma. • Normal spirometry and respond to inhaled and systemic corticosteroids. • Can be ruled out if induced sputum contains insufficient eosinophils (less than 3 percent) or if corticosteroid therapy does not improve the cough. • The condition may be transient, episodic, or persistent unless treated. Rarely, patients may require long-term treatment with prednisone.

14. POSTINFECTIOUS COUGH • Consider when cough persists after an upper respiratory tract infection. • Self-limited and will resolve spontaneously, although it may persist for three or more months. • Reassurance is a good approach in otherwise healthy patients. • Oral or inhaled corticosteroids, ipratropium (Atrovent), or cough suppressants may be prescribed to help with sleep.

15. CHEMICAL IRRITANTS • Chronic bronchitis caused by exposure to cigarette smoke or other irritants is an important cause of chronic cough. • Cigarette smoking is the most common risk factor for chronic obstructive pulmonary disease. • Although chronic bronchitis is a relatively common cause of chronic cough, it accounts for only 5 percent of patients who present for evaluation and treatment. • The initial treatment is eliminating the patient's exposure to irritants.

16. PSYCHOGENIC OR HABITUAL COUGH • Diagnosis of exclusion • Patients with this condition do not cough during sleep, are not awakened by cough, and generally do not cough during enjoyable distractions. • Failure to cough during sleep is not specific for this condition. • Common triggers include changes in ambient temperature; taking a deep breath; laughing; talking on the telephone for more than a few minutes; exposure to cigarette smoke, aerosol sprays, or perfumes; or eating crumbly, dry food.

17. Patients with Abnormal CXR • If chest radiography reveals abnormalities, further tests may be required to establish a diagnosis. • Possible studies include high-resolution computed tomography of the chest, pulmonary function testing, barium esophagography, cardiac studies, and bronchoscopy. • Referral to a pulmonologist or cardiothoracic surgeon may be required to obtain a definitive diagnosis for detected lesions.

18. BRONCHIECTASIS • Cough is associated with excessive overproduction and reduced clearance of airway secretions • Can be associated with UACS, asthma, GERD, and chronic bronchitis. • CXR may demonstrate increased thickening of the bronchial wall. • Etiologies include: postinfectious and idiopathic causes; genetic disease (e.g., cystic fibrosis, primary ciliary dyskinesia, α1-antitrypsin deficiency); aspiration or GERD; immune deficiency; rheumatoid arthritis; ulcerative colitis; and allergic bronchopulmonary aspergillosis.

19. BRONCHOGENIC CARCINOMA • CT should be ordered if chest radiography findings suggest malignancy. • A patient with persistent symptoms despite having normal chest radiography and a negative evaluation for common causes of cough should also be evaluated with CT or bronchoscopy. • Sputum samples can be examined for the presence of cancer cells.

20. TUBERCULOSIS • Consider in patients with chronic cough who have sputum production, hemoptysis, fever, or weight loss and who live in areas with a high prevalence of the disease, and in those at high risk (e.g., HIV, IVD). • These patients may have normal physical examination and chest radiography findings, so additional testing (e.g., skin testing, sputum culture) may be needed to make the diagnosis.

21. SARCOIDOSIS • Patients typically have CXR findings suggestive of the diagnosis (i.e., mediastinal widening caused by bilateral hilar adenopathy and reticular opacities).

22. Chronic Cough in Children • Cough lasting longer than four weeks is considered chronic. • The most common causes of chronic cough in children are asthma, respiratory tract infections, and GERD. • The differential diagnosis for chronic isolated cough without associated wheezing in an otherwise healthy child includes recurrent viral bronchitis, postinfectious cough, pertussis-like illness, cough-variant asthma, UACS, psychogenic cough, and GERD.

23. Worrisome Cough in Children • Neonatal onset of cough • Chronic moist or purulent cough • Cough starting with and persisting after a choking episode • Cough occurring during or after feedings, or associated failure to thrive.

24. Chronic Cough in Children • The pathway recommended for investigating chronic cough in adults is not suitable for children younger than 15 years. • Children with chronic cough should undergo chest radiography and spirometry, at minimum. • Foreign body aspiration should be considered in young children. • Congenital conditions, cystic fibrosis, and immune disorders are possible diagnoses in children with chronic cough and recurrent infections. • Congenital abnormalities, although rare, can include vascular rings, tracheoesophageal fistulas, and primary ciliary dyskinesia.

27. Evaluation of Suspected Dementia • Epidemiology • After 65 years of age, the lifetime risk of developing dementia is approximately 17 to 20 % • 70 % of patients with dementia have Alzheimer disease • 17 % have vascular dementia • 13 % have a combination of dementia with Lewy bodies, Parkinson-related dementia, alcoholic dementia, or frontal lobe dementia • 10 to 15 % of patients with mild cognitive impairment, which is defined as memory impairment without meeting criteria for dementia, will develop Alzheimer disease. • AD affects 5.3 million Americans, and is the sixth leading cause of death • Median survival time after diagnosis of dementia is 4.5 years.

28. Risk Factors • Age • Family history of dementia • Apolipoprotein E4 genotype • Cardiovascular comorbidities • Chronic anticholinergic use • Lower educational level • In persons 71 to 79 years of age, the prevalence is approximately 5% • 37% in persons > 90 years

29. NIA/AA Diagnostic Guidelines • Dementia can be diagnosed if cognitive or behavioral symptoms interfere with the patient's ability to function at work or socially, if there is a decline from previous functioning, and if cognitive or behavioral impairments are detected through a combination of history and cognitive assessment • Impairments must be present in at least two of the following domains: ability to recall new information, reasoning, visuospatial ability, language, and personality. • Mild cognitive impairment is defined as impairment in at least one of these domains; concern about cognition as expressed by the patient, an informant, or the physician; and preservation of independence and the ability to work

30. Initial History and Functional Assessment • Obtain history from the patient and from a family member or caregiver, include specifics of cognitive deficit, time of onset, and speed of progression. • Assess the extent of impairment in instrumental activities of daily living: managing money and medications, shopping, housekeeping, cooking, and transportation. • In the early stages of dementia, IADLs that require calculation and planning, are often the first to become impaired. • Basic activities of daily living, such as dressing, eating, toileting, and grooming, are generally intact in early dementia and do not become impaired until later in the disease progression.

33. At the Second Visit • Further cognitive testing with either • MMSE (30 items, assesses 6 domains, SN 71-92%, SP 56-96%, affected by education level, above 24 is normal) • MoCA (assesses 9 domains, total possible score is 30 points; a score of 26 or above is considered normal, has higher SN in detecting MCI 90% and early AD 100%)

37. Heel Pain • Common presenting symptom in ambulatory clinics. • There are many causes, but a mechanical etiology is most common. • Location can be a guide to the proper diagnosis.

44. PMS and PMDD • PMS is defined as recurrent moderate psychological and physical symptoms that occur during the luteal phase of menses and resolve with menstruation. • Affects 20 to 32%of premenopausal women. • Women with PMDD experience affective or somatic symptoms that cause severe dysfunction in social or occupational realms. • Affects 3 to 8% of premenopausal women

46. Etiology • Women w/ PMS/PMDD are more physiologically sensitive to and express more symptoms with normal cycling levels of estrogen and progesterone. • Increases in aldosterone and plasma renin activity are the hypothetical mechanisms for fluid retention and bloating symptoms. • Neurotransmitters, particularly serotonin and γ-amino-butyric acid, appear to be involved. • Twin concordance studies suggest a genetic predisposition.

49. Differential Diagnosis • Depression, anxiety, hypothyroidism, anemia, endometriosis, or physiologic ovarian cysts • ACOG suggests diagnosing PMS based on prospective symptom diaries over 2 consecutive symptomatic cycles. • Daily Record of Severity of Problems has negative predictive value (83.4 percent).