The diagnosis and management of chronic cough.
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Biomedical subjects
Publications and source records attributed to M Pistolesi.
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The pathogenesis and clinical features of gastro-oesophageal reflux related cough are complex and the diagnostic tests available are of limited reliability. Treatment needs to be tailored to the specific needs of individual patients and other possible causes of chronic cough should be investigated. Treatment should only be considered to have failed when cough persists after administration of proton pump inhibitors at an adequate dosage for a sufficient length of time.
Pulmonary embolism (PE) is more often diagnosed post mortem by pathologists than in vivo by clinicians. The identification of practical diagnostic algorithms could reduce the rate of diagnoses first made at autopsy. The literature was reviewed for evidence-based approaches to PE diagnosis. Since the PE mortality rate greatly exceeds that of deep vein thrombosis (DVT), more emphasis was given to reports specifically dealing with PE diagnosis by objective pulmonary vascular imaging techniques than to those aimed at DVT detection. Several studies have shown that standardized clinical estimates can be effectively used to give a pretest probability to calculate, after appropriate objective testing, the post-test probability of PE. A prospective trial has shown that perfusion scanning, rather than ventilation/perfusion scanning, should be the imaging technique of first choice for the management of patients suspected of having PE. The clinical usefulness of spiral computed tomography has not as yet been firmly established. However, ongoing technological developments would probably render the technique accurate enough to replace conventional angiography. The authors propose a noninvasive diagnostic algorithm with high predictive accuracy (positive predictive value 96%; negative predictive value 98%) starting with a standardized assessment of clinical likelihood, followed by a perfusion scan and, eventually, spiral computed tomography in only a minority of patients (< 20%) with discordant clinical and scintigraphic findings.
PURPOSE: Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE. SUBJECTS AND METHODS: We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE. RESULTS: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively. CONCLUSIONS: In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.
OBJECTIVE: To investigate the prevalence and features of asymptomatic pulmonary involvement in juvenile dermatomyositis (JDM). METHODS: Twelve JDM patients underwent pulmonary function tests at baseline, 12 and 24 months. Disease activity, duration, serum lactate dehydrogenase (LDH) values and antinuclear antibody (ANA) titres were also evaluated. RESULTS: Five patients showed lung impairment at baseline and four at 12 and 24 months. Forced expiratory volume in 1s, forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and alveolar volume were the most frequently altered variables, indicating a restrictive pattern and impairment of diffusion. The prevalence and features of pulmonary alterations did not change during follow-up. FVC values were significantly lower in active JDM patients and were inversely related to LDH. DLCO values were significantly lower in ANA-positive patients. About half of the patients of this small case series of JDM had asymptomatic lung disease. CONCLUSIONS: We suggest that lung function should be evaluated at disease onset and regularly during follow-up, as pulmonary function tests can detect otherwise unpredictable pulmonary involvement.
Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.
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Clinical assessment is a cornerstone of the recently validated diagnostic strategies for pulmonary embolism (PE). Although the diagnostic yield of individual symptoms, signs, and common laboratory tests is limited, the combination of these variables, either by empirical assessment or by a prediction rule, can be used to express a clinical probability of PE. The latter may serve as pretest probability to predict the probability of PE after further objective testing (posterior or post-test probability). Over the last few years, attempts have been made to develop structured prediction models for PE. In a Canadian multicenter prospective study, the clinical probability of PE was rated as low, intermediate, or high according to a model which included assessment of presenting symptoms and signs, risk factors, and presence or absence of an alternative diagnosis at least as likely as PE. The prevalence of PE in the low, intermediate, and high pretest probability categories was 3, 28, and 78%, respectively. This model relies heavily on the clinician's subjective judgement as to whether an alternative diagnosis is as likely as or more likely than PE, and, as such, it can be hardly standardized. Furthermore, the inherent complexity of the model may limit its applicability in daily clinical practice. Recently, a simple clinical score was developed to stratify outpatients with suspected PE into groups with low, intermediate, or high clinical probability. Logistic regression was used to predict parameters associated with PE. A score =/<4 identified patients with low probability of whom 10% had PE. The prevalence of PE in patients with intermediate (score 5-8) and high probability (score > or = 9) was 38 and 81%, respectively. As opposed to the Canadian model, this clinical score is standardized. The predictor variables identified in the model, however, were derived from a data base of emergency ward patients. This model may, therefore, not be valid in assessing the clinical probability of PE in inpatients. In the PISA-PED study, a clinical diagnostic algorithm was developed which rests on the identification of three relevant clinical symptoms and on their association with electrocardiographic and/or radiographic abnormalities specific for PE. Among patients who, according to the model, had been rated as having a high clinical probability, the prevalence of proven PE was 97%, while it was 3% in those with low probability. The prevalence of PE in patients with intermediate clinical probability was 41%. These results underscore the importance of incorporating the standardized reading of the electrocardiogram and of the chest radiograph into the clinical evaluation of patients with suspected PE. The interpretation of these laboratory data, however, requires experience. Future research is needed to develop standardized models, of varying degree of complexity, which may find application in different clinical settings to predict the probability of PE.
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The effects of spacer devices on the magnitude and velocity of large and small airway bronchodilator responses in asthmatic patients who can correctly operate a metered dose inhaler (MDI) remain unclear. According to a double-blinded, randomized, crossover protocol, 14 asthmatic patients were studied on seven separate occasions. On each occasion, patients inhaled doubling methacholine concentrations until forced expiratory volume in 1 second (FEV1) had fallen by 20% of baseline. Changes in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) were also evaluated. Subsequently, patients were administered 20 or 50 micrograms of procaterol from an MDI either alone or in conjunction with a small- or large-volume spacer device. Changes in FEV1 and FEF25-75 corrected for baseline forced vital capacity (isoFEF25-75) were assessed at 3-minute intervals for 15 minutes and at 30 minutes. Spontaneous recovery was similarly evaluated. The time required to attain significant increases in both FEV1 and isoFEF25-75 was calculated in bronchodilator trials. With 20 micrograms of procaterol, both spacers allowed larger and faster FEV1 increases than the MDI alone (P < 0.01); with 50 micrograms, the velocity and magnitude of FEV1 increases were further enhanced in trials with the MDI alone. The lower procaterol dose via the large-volume spacer determined larger and faster isoFEF25-75 increases than the higher dose via both the small-volume spacer and the MDI alone (P < 0.01). Spacers enhance bronchodilation even in patients using MDIs optimally. Compared with both the small-volume device and the MDI alone, the large-volume spacer allows faster and larger small airway dilation with less than half of the procaterol dose.
To provide clinical diagnostic criteria for pulmonary embolism (PE), we evaluated 750 consecutive patients with suspected PE who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Prior to perfusion lung scanning, patients were examined independently by six pulmonologists according to a standardized diagnostic protocol. Study design required pulmonary angiography in all patients with abnormal scans. Patients are reported as two distinct groups: a first group of 500, whose data were analyzed to derive a clinical diagnostic algorithm for PE, and a second group of 250 in whom the diagnostic algorithm was validated. PE was diagnosed by angiography in 202 (40%) of the 500 patients in the first group. A diagnostic algorithm was developed that includes the identification of three symptoms (sudden onset dyspnea, chest pain, and fainting) and their association with one or more of the following abnormalities: electrocardiographic signs of right ventricular overload, radiographic signs of oligemia, amputation of hilar artery, and pulmonary consolidations compatible with infarction. The above three symptoms (singly or in some combination) were associated with at least one of the above electrocardiographic and radiographic abnormalities in 164 (81%) of 202 patients with confirmed PE and in only 22 (7%) of 298 patients without PE. The rate of correct clinical classification was 88% (440/500). In the validation group of 250 patients the prevalence of PE was 42% (104/250). In this group, the sensitivity and specificity of the clinical diagnostic algorithm for PE were 84% (95% CI: 77 to 91%) and 95% (95% CI: 91 to 99%), respectively. The rate of correct clinical classification was 90% (225/250). Combining clinical estimates of PE, derived from the diagnostic algorithm, with independent interpretation of perfusion lung scans helps restrict the need for angiography to a minority of patients with suspected PE.
Ablation of the larynx implies withdrawal of afferent information from receptors involved both in the control of expiratory flow and in the genesis of protective airway reflexes including coughing. To investigate the effects of laryngectomy on the sensory and motor component of coughing, maximal voluntary cough (MVC) efforts as well as the reflex cough (RC) responses at threshold (T) and suprathreshold (1.8 x T, ST) levels induced by inhalation of progressively increasing concentrations of ultrasonically nebulized distilled water (fog) were analyzed in 10 laryngectomized patients and 10 control subjects. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGP) and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity (IEMGP/TEC). Cough peak flow was also recorded. Cough threshold was similar in patients and controls, as were IEMGP, TEC, and IEMGP/ TEC recorded during MVC and RCST. In contrast, during RCT, patients' IEMGP was significantly reduced (p < 0.05), thus leading to a significant decrease in IEMGP/TEC (p < 0.05) even in the absence of significant differences in TEC. Cough flow closely correlated with IEMG-related variables. Cough volume acceleration, i. e., the ratio of cough peak flow to the corresponding time to cough peak flow was also significantly reduced in the patients, especially during RCT (p < 0.01). The results suggest that the lack of signals arising from the larynx may result in a reduction of cough volume acceleration as well as in the intensity of abdominal muscle contractions during RCT. These factors may contribute to facilitate the onset and/or the persistence of chest infections in laryngectomized patients.
OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal scans who had normal P(A-a)O2, PaO2 and PaCO2 were 20, 25 and 37%, respectively. No differences were observed in the mean values of arterial blood gas data between patients with pulmonary embolism and those who had abnormal scans and negative angiograms. Among the 773 patients with suspected pulmonary embolism, 364 (47%) had prior cardiopulmonary disease. Pulmonary embolism was diagnosed in 151 (41%) of 364 patients with prior cardiopulmonary disease, and in 161 (39%) of 409 patients without prior cardiopulmonary disease. Among patients with pulmonary embolism, there was no difference in arterial blood gas data between patients with and those without prior CPD. CONCLUSION: These data indicate that arterial blood gas tests are of limited value in the diagnostic work-up of pulmonary embolism if they are not interpreted in conjunction with clinical and other laboratory tests.
OBJECTIVE: Pleuropulmonary involvement in adult spondyloarthropathy (SpA) has been thoroughly investigated. SpA is usually detected by conventional radiology as fibrosis of the upper lobes in about 30% of asymptomatic patients. Pulmonary function tests (PFT) reveal decreased vital capacity and total lung capacity, as well as increased residual volume. Juvenile SpA (JSpA) is a rare clinical condition, and no extensive investigations have been carried out on pulmonary involvement in JSpA. We studied prevalence and features of PFT alterations in patients with JSpA over a 2 year followup and analyzed the relationship between PFT and disease duration, disease activity, and chest and spine mobility. METHODS: Eighteen patients with JSpA, with no clinical signs of lung disease and normal chest radiographs, underwent PFT--static and dynamic volumes, diffusing capacity for carbon monoxide (DLCO), at enrollment (T0), at 12 months (T1), and at 24 months later (T2). Disease activity was defined at each investigation by clinical and hematological data. RESULTS: Significant functional lung impairment was detected in 33% of patients (reduced forced vital capacity in 22% and DLCO in 11%). No significant change in the prevalence and features of PFT alterations was detected at T1 and T2; no relationship was found between PFT and duration, activity, and clinical scores of the disease. CONCLUSION: Thirty-three percent of JSpA patients without clinical symptoms and no radiological findings of lung involvement show PFT alterations, mainly characterized by a restrictive pattern. No progression or modification in PFT developed over 2 years. No correlation was found between PFT and disease duration, activity, and clinical scores.
Cough-related variables such as cough frequency, time to onset (i.e. the time until the first cough occurs) and the cough index (i.e. the ratio between the cough frequency and the time to onset) may be important when interpreting results of cough challenges for therapeutic interventions or for comparative research purposes. Nevertheless, repeatability (or reproducibility) for these widely used variables has been poorly studied. In thirty normal subjects, coughing was induced by inhalation of threshold (T) and suprathreshold (1.6 x T) concentrations of ultrasonically nebulized distilled water (fog). Cough threshold was taken as the lowest fog concentration that evoked at least one cough effort during two challenges separated by a 30-min interval. During challenges performed at both threshold and suprathreshold stimulus intensity, cough frequency, time to onset, and the cough index were assessed; within-subject repeatability for these variables was subsequently evaluated. Median +/- interquartile range cough threshold value was 0.9+/-0.5 mL x min(-1). During the two challenges performed to assess cough threshold, the mean +/-SD values of cough frequency, time to onset, and cough index were similar (5.0+/-2.7 and 5.3+/-3.1 coughs x min(-1), 32.4+/-13.3 and 32.9+/-13.6 s, and 0.2+/-0.2 and 0.2+/-0.2, respectively). However, none of these cough-related variables proved to be sufficiently repeatable. During the two challenges performed at suprathreshold stimulus intensity, mean values of cough frequency, time to onset, and cough index were also similar (20.0+/-9.0 and 18.2+/-10.2 coughs x min(-1), 13.5+/-5.8 and 12.0+/-4.62 s, and 1.7+/-1.0 and 1.8+/-1.2); furthermore, all considered variable of suprathreshold challenge turned out to be reproducible. In conclusion, during fog challenges at threshold stimulus intensity, cough frequency, time to onset and cough index cannot reliably be used for evaluating cough responses. However, these cough-related variables may represent useful and reliable research tools in the evaluation of suprathreshold cough responses.
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Pulmonary embolism (PE) remains a challenging diagnostic problem because it mimics other cardiopulmonary disorders. Pulmonary angiography is still the reference standard for diagnosing PE but it is costly, invasive and not readily available. Non-invasive diagnostic strategies have therefore been developed to forego pulmonary angiography in patients suspected of having PE. Ventilation/perfusion lung scanning is, at present, the most widely used non-invasive diagnostic test for PE. A high probability ventilation/perfusion scan (segmental or greater perfusion defects with normal ventilation) warrants the institution of anticoagulant therapy especially when paired with high clinical suspicion of PE. Yet, only a minority of patients with confirmed PE have high probability ventilation/perfusion scans. Ventilation/perfusion abnormalities other than those of the high probability scan should be regarded as non-diagnostic. Under these circumstances, documentation of deep vein thrombosis by non-invasive leg testing warrants anticoagulation without the need for angiography. However, a single negative venous study result does not permit to rule out PE in patients with non-diagnostic ventilation/perfusion scans. Results of a recent prospective study indicate that accurate diagnosis or exclusion of PE is possible with perfusion lung scanning alone (without ventilation imaging). Combining perfusion lung scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected PE.
Combined resection of primary non-small-cell lung cancer and single brain metastasis is reportedly superior to other treatments in prolonging survival and disease-free interval. To identify prognostic factors that influenced survival we reviewed clinical records and follow-up data of 52 consecutive patients with non-small-cell lung cancer and single brain metastasis who had been evaluated for combined lung and brain operation: 19 had synchronous and 33 metachronous non-small-cell lung cancer and single brain metastasis. Seven patients were excluded from combined operation because of either early brain relapse after craniotomy or single brain metastasis localization in deep brain structures. Forty-one of the 45 patients who underwent combined operation had complete remission of neurologic symptoms. Actuarial 5-year survival from the second surgical intervention was 16% (median 19 months, range 1 to 104 months). N0 status and lobectomy were the only variables associated with longer survival. Actuarial 5-year survivals in patients with synchronous and metachronous presentation were 6.6% and 19%, respectively. In patients with metachronous presentation the length of survival was significantly associated with N0 status, lobectomy, and interval between lung and brain operation equal to or longer than 14.5 months. The subset of patients with N0 status and interval between operations longer than 14.5 months had a 61% 5-year survival. None of the patients with N1-2 disease and shorter interval between operations was alive at 20 months. These data indicate that prognostic factors may help to identify subsets of patients with markedly different outcomes after combined lung and brain operation.