Thaddeus Bartter

An Algorithmic Approach to Chronic Cough

Chronic cough is an important medical and economic problem. The prevalence of chronic cough in the United States among nonsmoking adults is reported to range from 14% to 23% [1, 2]. Not only is the symptom itself problematic, but it raises concerns about possible serious underlying disease [3]. Chronic cough is the fifth most common symptom seen by outpatient physicians [4] and is estimated to be the primary reason for 30 million physician visits annually [4]. In the United States alone, approximately

Marijuana and lung diseases.

600 million per year are spent on prescription and over-the-counter antitussives [5]. Major advances in the clinical approach to chronic cough have been made during the last 15 years. In a 1977 review [6], Irwin and colleagues proposed an approach to chronic cough based on the anatomic locations of the receptors and afferent pathways involved in the cough reflex. Using such an approach, Irwin and colleagues reported in 1981 [7] and again in 1990 [8] that the cause of chronic cough could be determined 100% of the time and that subsequent cause-specific treatment was almost always successful. The postnasal drip syndrome, mainly from chronic rhinitis, was the most common cause, followed by asthma [7, 8]. These two diagnoses, alone or in combination, accounted for cough in 75% of the patients [7, 8]. Gastroesophageal reflux was the next most common cause [7, 8]. Poe and colleagues [9] also reported that the postnasal drip syndrome or asthma caused chronic cough in most of their patients. We evaluated a sequential, stepped approach to chronic cough, emphasizing initial treatment of all patients with an antihistamine-decongestant for possible postnasal drip syndrome caused by rhinitis. We also determined the value of routine bronchoprovocation challenge for predicting whether asthma was a causative factor in cough. Methods Patient Selection All patients who came to our university-based pulmonary practice with a chief complaint of chronic cough were considered for inclusion in the study. Cough was considered to be chronic if it had been present for 3 weeks or longer [7, 8]. The following were exclusion criteria: 1) immunocompromise, including known lung cancer or other active malignancy, the acquired immunodeficiency syndrome, or current treatment with corticosteroids or other immunosuppressive agents; 2) cigarette use within 12 months; 3) use of an angiotensin-converting-enzyme inhibitor within 4 weeks; and 4) contraindication to the use of an antihistamine-decongestant or to bronchoprovocation challenge, including pregnancy and an FEV1 less than 70% of predicted value. Algorithm The approach involved a standardized initial evaluation, weekly follow-up, a series of sequential diagnostic and therapeutic steps, and a predefined end point. Initial Evaluation The initial evaluation included a history; physical examination; review of previous diagnostic studies; and a questionnaire on the duration, frequency, and severity of cough, postnasal drip symptoms, dyspnea, wheeze, and symptoms of gastroesophageal reflux. Spirometry was done next, followed by a methacholine bronchoprovocation challenge using a modification of the method of Hargreave and colleagues [10]. Bronchial hyper-responsiveness was defined as a 20% decrease in the FEV1 (Pc 20) at a methacholine concentration of 8 mg/mL or more [11]. Because of its low yield in previous studies [7-9], a chest roentgenogram was not included in the initial evaluation unless there was clinical suspicion of infection or neoplasm (such as fever, weight loss, or hemoptysis). Weekly Follow-up Patients were contacted by phone each week and seen in person whenever clinically necessary. We created a standardized scale for the patient to use in rating weekly cough severity and a second scale for rating side effects of therapy. The cough severity scale ranged from 0 (cough gone) to 7 (cough markedly worse). The descriptors for the scale are shown in Figure 1. Side effects were rated as none, mild, moderate, or severe (intolerable). Figure 1. Response to 1 week of antihistamine-decongestant therapy. End Point The end point for treatment was cough resolution, defined as a patient report of complete absence of cough for 2 consecutive weeks or of diminution to the point that the patient considered the cough insignificant. Step 1 An antihistamine-decongestant preparation containing 1 mg of azatadine maleate plus 120 mg of sustained-release pseudoephedrine sulfate (Trinalin, Key Pharmaceuticals Inc.; Kenilworth, New Jersey) was prescribed to be taken twice daily as empiric therapy for possible postnasal drip syndrome caused by rhinitis (postviral, allergic, or vasomotor). If the cough did not improve at the end of 1 week of antihistamine-decongestant therapy, step 2 was begun immediately. If the cough improved after 1 week of therapy, antihistamine-decongestant alone was continued either until it resolved or until no further improvement occurred. At that point, patients with persistent symptoms of the postnasal drip syndrome (sensation of postnasal drip, throat clearing, nasal congestion, or a tickle in the back of the throat) were given nasal corticosteroids in addition to the antihistamine-decongestant. Sinus imaging was obtained before nasal corticosteroids were prescribed if chronic sinusitis was suspected or subsequently if postnasal drip persisted despite the combination of antihistamine-decongestant and nasal corticosteroid therapy. Patients with sinus roentgenograms consistent with sinusitis (sinus opacification, air-fluid levels, or mucosal thickening) were treated with twice daily oxymetazoline hydrochloride nasal spray (Afrin, Schering-Plough HealthCare Products; Memphis, Tennessee) for 3 days, nasal corticosteroids twice daily, antihistamine-decongestant twice daily, and antibiotics for as long as 6 weeks. If cough still persisted, a computed tomographic study of the sinuses was obtained. If substantial abnormalities were present, the patient was referred for an otolaryngologic evaluation and possible sinus surgery. Substitutions for Trinalin could be made at any time if severe side effects developed. For severe drowsiness, astemizole (Hismanal, Janssen Pharmaceutica, Piscataway, New Jersey), 10 mg once daily, plus pseudoephedrine, 60 mg twice daily, were substituted. For severe insomnia, jitteriness, or urinary obstruction, astemizole once daily plus nasal corticosteroids twice daily were substituted. Step 2 Patients who were still coughing after step 1 were next evaluated for asthma. Because the treatment was the same, no attempt was made to distinguish between asthma and postviral bronchial hyper-responsiveness [12]. Patients who had bronchial hyper-responsiveness on bronchoprovocation challenge were treated for 1 week with an inhaled 2-agonist, albuterol, two puffs four times a day via metered-dose inhaler. If cough persisted, prednisone therapy (1 mg/kg body weight per day [maximum, 60 mg/d]) was added to the albuterol for a week. An oral 2-agonist or theophylline was substituted for the inhaled albuterol if a patient reported marked cough in response to inhaled albuterol. Step 3 Patients who continued to have persistent cough next had chest and sinus roentgenograms if they had not already been obtained. Any abnormalities considered to be clinically significant were evaluated and treated. If no significant abnormalities were found or the patient continued to cough despite appropriate therapy, the patient was advanced to step 4. Step 4 Patients were next evaluated for gastroesophageal reflux. Patients with symptoms consistent with gastroesophageal reflux first had a 2-week trial of therapy with ranitidine, 150 mg twice daily, along with antireflux measures (no eating or drinking for at least 2 hours before going to bed or lying down, 20-cm elevation of the head of the bed using blocks, and avoidance of caffeine, alcohol, chocolate, and other foods known to exacerbate gastroesophageal reflux). Lack of a response to the 2-week trial of ranitidine led to a 24-hour esophageal pH-probe study. Patients without symptoms of gastroesophageal reflux had 24-hour esophageal pH-probe monitoring before therapy for gastroesophageal reflux was begun. pH-probe monitoring was performed and interpreted according to the criteria of Demeester and colleagues [13]. All patients whose pH-probe studies showed pathologic gastroesophageal reflux were treated for at least 8 weeks with omeprazole, 20 mg daily, in addition to antireflux measures. An upper gastrointestinal barium swallow or a gastroenterology consultation or both were obtained if the patient had any persistent gastrointestinal complaints. Step 5 Patients who continued to cough next had bronchoscopy. If the bronchoscopy was nondiagnostic, the patient was treated (or retreated) with asthma therapy even if the bronchoprovocation challenge had been negative or if 2-agonist and prednisone therapy was previously ineffective. If cough persisted, uncommon causes were considered (Table 1) [6-9]. Psychogenic cough was considered a diagnosis of exclusion. Table 1. Uncommon Causes of Chronic Cough Three-Month Follow-up All patients were reevaluated using a standardized questionnaire 3 months after cough had resolved to determine whether cough had recurred and whether they were still taking cough-specific medications. Final Diagnostic Criteria No cause of cough was considered definitive until treatment for that cause had been effective (that is, was associated with marked improvement or resolution). When therapy for only one diagnosis resolved the cough, that diagnosis was considered to be the sole cause of cough. When therapy for a diagnosis effected marked improvement short of resolution, that diagnosis was considered to be one of the causes of cough and treatment was continued while additional diagnoses were investigated. Statistical Analysis Recurring data were analyzed by paired t-tests. The extent of association between two variables in a cross-tab

High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer

Purpose of review Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Recent findings Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. Summary There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

Lung Sound Analysis in the Diagnosis of Obstructive Airway Disease

BACKGROUND Conventional nutritional supplements are not or only partly successful in inducing protein accretion in advanced cancer, suggesting an attenuated anabolic response. To prevent muscle wasting and its deleterious consequences, generating an anabolic response is crucial. Dietary essential amino acids (EAA) have anabolic properties in other wasting diseases; however, data in advanced cancer are lacking. PATIENTS AND METHODS In 13 patients with advanced nonsmall-cell lung cancer (NSCLC) (stage III and IV) and 11 healthy age-matched subjects, we measured protein synthesis and breakdown of the whole body, and net protein anabolism (difference between protein synthesis and breakdown) after intake of 14 g of free EAA with high leucine levels (EAA/leucine) versus a balanced amino acid mixture containing both EAA and non-EAA as present in whey protein, according to a randomized, double-blind, crossover design. RESULTS Protein synthesis and net protein anabolism were higher after intake of the EAA/leucine than the balanced amino acid mixture (P < 0.001), independent of presence of cancer. A highly significant linear relationship between net protein anabolism and the amount of EAA available in the systemic circulation (R(2): 0.85, P < 0.001) was found in both groups. The presence of muscle or recent weight loss, systemic inflammatory response, or length of survival did not influence this relationship. High leucine levels in the EAA/leucine mixture was of no anabolic benefit. CONCLUSIONS There is no anabolic resistance or attenuated anabolic potential to intake of 14 g of EAA/leucine or balanced amino acid mixture in advanced (mainly stage III) NSCLC. The high anabolic potential of dietary EAA in cancer patients is independent of their nutritional status, systemic inflammatory response or disease trajectory, suggesting a key role of EAA in new nutritional approaches to prevent muscle loss, thereby improving outcome of patients with advanced cancer. CLINICALTRAILSGOV NCT01172314.

Symptom burden in chronic obstructive pulmonary disease and cancer.

Background: Dyspnea is prevalent and has a broad differential diagnosis. Difficulty in determining the correct etiology can delay proper treatment. Non-invasively obtained acoustic signals may offer benefit in identifying patients with dyspnea due to obstructive airway disease (OAD). Objectives: The aim of this pilot study was to determine whether patients with acute dyspnea due to OAD had distinguishing features when studied with a computerized acoustic-based imaging technique. Methods: Respiratory sounds from patients with dyspnea due to OAD (n = 32) and those with dyspnea not due to OAD (n = 39) were studied and compared with normal controls (n = 16). Results: In patients without OAD and in controls, the ratios of peak inspiratory to peak expiratory vibration energy values (peak I/E vibration ratio) were remarkably similar, 6.3 ± 5.1 and 5.6 ± 4, respectively. For the OAD patients, the peak I/E vibration ratio was significantly lower at 1.3 ± 0.04 (p < 0.01). In the patients without OAD and the controls, the ratios of inspiratory time to expiratory time (I/E time ratio) were again similar, 1.0 ± 0.1 and 0.99 ± 0.11, respectively. For the OAD patients, the I/E time ratio was significantly lower at 0.72 ± 0.19 (p < 0.01). Conclusions: This modality was useful in identifying patients whose dyspnea was due to OAD. The ability to objectively and non-invasively measure these differences may prove clinically useful in distinguishing the operant physiology in patients presenting with acute dyspnea.

Rapid opiate detoxification

Purpose of review Chronic obstructive pulmonary disease (COPD) is a crippling disease with a high worldwide prevalence. The purpose of this review is to highlight recent studies which define the global impact of COPD on quality of life. There are direct implications for care. Recent findings Dyspnea is a dominant and defining symptom for patients with COPD, but the overall degree of impairment suffered by patients with COPD extends far beyond shortness of breath. A series of recent studies gives us insight into both the physical and the psychosocial burdens of the disease and their negative net effects upon quality of life. The suffering of patients with COPD is similar to that of patients with cancer, and palliative measures have been shown to be an important component of comprehensive care. Summary The symptom burden in patients with severe COPD is high and is comparable to that of patients with cancer. Ironically, patients with COPD could be said to suffer more than those with cancer; the symptom burden is similar, but patients with COPD tend to live longer. The literature is replete with evidence that a palliative care approach to patients with cancer increases the quality of life (and perhaps even the quality of death). The same palliative care approach can and should be used for patients with COPD. There are now objective data to support the benefits of such an approach.

An algorithmic approach to chronic dyspnea

We report on clinical and practical aspects of treatment of opiate addiction with a relatively new approach, rapid opiate detoxification (ROD). The goal is to induce rapid narcotic withdrawal in a controlled environment using narcotic antagonists while suppressing withdrawal symptoms with sedative drugs, thus effecting a dramatic abbreviation of the traditional withdrawal schedule. Twenty-five consecutive heroin-addicted patients presenting for detoxification were treated at a university hospital. There were 14 women and 11 men, with a mean age 32.6 years (range, 24-48). They underwent 29 separate detoxifications over a 4-month period. All but 3 of the detoxifications were effected with ROD. Several different techniques were used over the 4-month period, ranging from intramuscular and oral sedation to intravenous sedation, paralysis, and intubation. Efficacy of detoxification was demonstrated for all patients undergoing ROD; all were given 50 mg of naltrexone PO prior to discharge, and none had withdrawal symptoms. (The three patients treated with abstinence were not so tested.) We derive three conclusions from this early clinical experience: First, ROD appears to be a valuable tool in the treatment of heroin addiction. ROD is an efficient, effective technique that can play an important role in an integrated rehabilitation program. Second, the optimal method of ROD is yet to be determined; a continuum of approaches is available. Third, ROD is probably most suited to designated outpatient centers.

Cough and asthma.

QUESTION The objective of the study was to prospectively evaluate an algorithmic approach to the cause(s) of chronic dyspnea. MATERIALS/PATIENTS/METHODS: Prospective observational study. The study group consisted of 123 patients with a chief complaint of dyspnea of unknown cause present for >8 weeks. Dyspnea severity scores were documented at entry and after therapy. Patients underwent an algorithmic approach to dyspnea. Therapy could be instituted at any time that data supported a treatable diagnosis. Whenever possible, accuracy of diagnosis was confirmed with an improvement in dyspnea after therapy. Tests required, spectrum and frequency of diagnoses, and the values of individual tests were determined. RESULTS Cause(s) was(were) diagnosed in 122/123 patients (99%); 97 patients had one diagnosis and 25 two diagnoses. Fifty-three percent of diagnoses were respiratory and 47% were non-respiratory. Following therapy, dyspnea improved in 63% of patients. CONCLUSIONS The prospective algorithmic approach led to diagnoses in 99% of cases. A third of patients were diagnosed with each tier of the algorithm, thus minimizing the need for invasive testing. Specific diagnoses led to improvement in dyspnea in the majority of cases. Based on the results of this study, the algorithm can be revised to further minimize unnecessary tests without loss of diagnostic accuracy.

Is chest tube insertion with ultrasound guidance safe in patients using clopidogrel

Purpose of review The intention of this article is to discuss and place into perspective recent articles on cough and asthma. Recent findings Asthma continues to be a major diagnosis in most studies of cough. The first prospective study of sub-acute cough demonstrated an asthma incidence lower than that for chronic cough, a logical finding; upper airway cough syndrome often causes cough in the postinfectious state. The first prospective study of cough in infants suggested asthma to be a minor cause of cough in infants, but methodological flaws make the conclusions uncertain. Efforts to separate cough-variant asthma from classic asthma continue. One group has demonstrated that the maximal bronchoconstrictor response in cough-variant asthma is blunted when compared with classic asthma, a possible explanation for the absence of wheeze and dyspnea in cough-variant asthma. Another look at airway resistance showed a less rapid rate of rise in resistance in cough-variant asthma with increasing methacholine dosing than in classic asthma. On the biochemical front, a group has demonstrated differences in vascular endothelial growth factor, which may be the underpinnings of differences between cough-variant asthma and classic asthma. Summary Recent data suggest that cough-variant asthma is part of a continuum in the expression of asthma symptoms and in the asthmatic inflammatory response.

Delay in diagnosis of chronic obstructive pulmonary disease: reasons and solutions.

Background and objective:  Drainage of the pleural space is a common procedure. The safety of chest tube insertion in patients using clopidogrel has not been investigated.