Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. METHODS AND RESULTS: Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. CONCLUSION: Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

A swollen face and neck after dental surgery: Think of subcutaneous emphysema and pneumomediastinum.

Pneumomediastinum and subcutaneous emphysema are defined as the pathological presence of free air in the mediastinum or subcutaneous tissue, respectively. In the majority of cases, pneumomediastinum is secondary to an iatrogenic cause, but has rarely been described after a routine dental extraction. This condition is generally self-limiting, but major complications can occur, such as mediastinitis, which is more frequently associated with iatrogenic pneumomediastinum. To highlight the importance of including this presumably underdiagnosed complication in the differential diagnosis, we present a case of a 50-year-old man with dysphagia, facial pain and swollen face and neck following a dental extraction.

The effect of nicotine patches on craving in the brain: A functional MRI study on heavy smokers.

BACKGROUND: Smoking is a common phenomenon and kills over 6 million people every year. Many smokers try to quit smoking by using nicotine replacement therapy (NRT). Most of the time, relapse occurs in less than six months after finishing the program of NRT. We performed a single blinded study in which our aim was to figure out what the effect of the nicotine patch is on craving in the brain of smokers deprived from smoking. METHODS: Five heavy smokers (Fagerström Test for Nicotine Dependence ≥4) underwent a functional magnetic resonance imaging (fMRI) in 4 random conditions: smoking (S); smoking deprivation (SD); SD combined with a NP (SD + NP); SD combined with a placebo patch (SD + PP). Visual stimulation provoked craving in block design by randomly displaying images of smoking related scenes. After image preprocessing, a fixed-effect analysis was performed to compare average group activations. The Questionnaire for Smoking Urges (QSU) was obtained before and after each scan. RESULTS: The fMRI results showed higher activation in areas involved in craving in S compared with SD + NP, SD + PP, and SD. In the SD + NP, limbic circuit and attention area were higher activated compared with SD and SD + PP. The SD + PP and SD showed higher activation in the frontal cortex and limbic system compared with S and SD + NP. Nonsmokers showed higher limbic activation compared with SD.The QSU increased significantly after the fMRI experiment in S (P = .036).The SD had higher QSU scores compared with the S before (P = .002), and also after (P = .022) the fMRI experiment. The NP showed lower scores than the SD before the experiment (P = .046). CONCLUSION: The fMRI experiment revealed lower activity in areas associated with attention when subjects were nicotine deprived (SD + PP and SD). Areas involved with craving showed less activity when nicotine is present (S and SD + NP). The QSU showed a significant difference between SD and when nicotine is present (S and SD + NP).

Fluorescein-enhanced autofluorescence thoracoscopy in patients with primary spontaneous pneumothorax and normal subjects.

RATIONALE: The exact site(s) and pathophysiology of air leakage in patients with primary spontaneous pneumothorax (PSP) are unknown. In one patient with PSP, fluorescein-enhanced autofluorescence thoracoscopy (FEAT) has shown areas of parenchymal abnormality unnoticed during white light thoracoscopy (WLT). OBJECTIVES: To prospectively perform and compare WLT and FEAT in patients with spontaneous pneumothorax and in normal subjects. METHODS: One-time FEAT and WLT inspection with systematic mapping of semiquantified lesions in 12 consecutive patients with PSP was compared with one-time FEAT and WLT during sequential bilateral thoracoscopy in 17 control subjects. RESULTS: WLT abnormalities (anthracosis, cobblestone malformation, and blebs/bullae) were more prevalent in PSP. FEAT, however, showed high-grade lesions in PSP only, which often were present at areas that were normal, or that only showed anthracosis at WLT. When blebs/bullae were present, bleb-associated FEAT abnormalities were only present in two. Actual fluorescein leakage was seen in two patients with PSP. CONCLUSIONS: Lungs in patients with PSP show significantly more abnormalities at WLT when compared with normal subjects. High-grade FEAT lesions were exclusively present in PSP, and predominantly at lung zones that appeared normal at white light inspection. These findings suggest that significant parenchymal abnormalities are not limited to lesions visible during WLT, such as blebs and bullae.

Factors determining altered perfusion after acute pulmonary embolism assessed by quantified single-photon emission computed tomography-perfusion scan.

AIM OF THE STUDY: The aim of the study was to analyze the evolution of perfusion (Q)-defects in patients treated for acute pulmonary embolism (PE), correlation with baseline parameters and evaluation of recurrence risk. METHODS: This is a single-center prospective observational cohort study in symptomatic normotensive PE. Comparison of the ventilation/perfusion single-photon emission computed tomography (V/Q-SPECT) acquired at baseline with a quantified SPECT (Q-SPECT) repeated at 1 week and 6 months. The Q-defect extent (percentage of total lung volume affected) was measured semiquantitatively. Data collected at baseline were age, gender, body mass index (BMI), history of previous venous thromboembolism (HVTE), Charlson's Comorbidity Score (CcS), plasma troponin-T and D-dimer levels, PE Severity Index, and tricuspid regurgitation jet (TRJ) velocity. RESULTS: Forty-six patients (22 men/24 women, mean age 61.7 years (± standard deviation 16.3)) completed the study. At 1 week, 13/46 (28.3 %) and at 6 months 22/46 (47.8%) patients had completely normalized Q-SPECT. Persistence of Q-defects was more frequent in female patients in univariate and multivariate analysis. We found no correlation between the persistence of Q-defects on Q-SPECT and HVTE, BMI, plasma troponin-T, and CcS. However, lower TRJ and younger age were statistically significantly linked to normalization of Q-scans after 6 months of treatment only in univariate analysis. There is no difference in the frequency of recurrent PE in relation to the persistence of Q-defects. CONCLUSION: Acute PE patients of female, older age, and higher TRJ in univariate analysis and patients of female in multivariate analysis seem to have a higher risk of persistent Q-defects after 6 months treatment. The presence of residual Q-abnormalities at 6 months was not associated with an increased risk for recurrent PE.

Successful treatment of a giant emphysematous bulla by bronchoscopic placement of endobronchial valves.

Surgical bullectomy is the treatment of choice for giant emphysematous bulla. We report a case of successful nonsurgical treatment with bronchoscopic placement of one-way endobronchial valves that are currently under investigation for the treatment of end-stage emphysema. In patients who are poor surgical candidates, this noninvasive bronchoscopic treatment may represent a valuable alternative.

Removal of covered self-expandable metallic airway stents in benign disorders: indications, technique, and outcomes.

STUDY OBJECTIVES: To describe the technique and outcome of removal of self-expandable metallic airway stents (SEMAS) in a series of patients who underwent stenting for benign airway stenoses. DESIGN AND SETTING: A retrospective cohort analysis of patients with benign airway disorders treated with SEMAS between 1997 and 2003, who presented with an indication for stent removal in a tertiary-care hospital, and referral interventional pulmonology clinic. PATIENTS AND METHODS: During the study period, 49 SEMAS were inserted in 39 patients for treatment of benign airway disorders. Ten of these 39 patients (25.6%), bearing 12 covered stents, presented with an indication for stent removal. Data of these cases were extracted from electronic files kept in our institution archive. RESULTS: Indications for stent removal included excessive or recurrent granuloma formation (five cases), recurrence of stenosis after stent failure (one case), stent fracture (two cases), and accomplishment of treatment (two cases). In all of these cases, covered versions of SEMAS had been placed either in the trachea or in a main bronchus. In contrast to many previous reports, these stents proved to be absolutely retrievable even if some difficulties were encountered. In all cases, however, removal was successful without major complications. All patients resumed normal spontaneous ventilation postoperatively, and follow-up was uneventful. Average duration of stenting before removal was 16.2 +/- 17.5 months (+/- SD) [range, 1 to 60 months]. CONCLUSIONS: We conclude that although placement of SEMAS is assumed to be permanent in patients with benign airway disorders, an indication for stent removal is often observed (25.6% in our series). The covered SEMAS can be effectively and safely removed if needed without major sequelae. Nevertheless, new technical improvements in metallic stent design and materials may help reinforce the concept of a retrievable metallic airway stent, which may offer significant clinical advantages.

Pulmonary embolism: current treatment options.

The initial treatment of patients with acute pulmonary embolism has traditionally involved unfractionated heparin. Given the more predictable pharmacodynamic and pharmacokinetic properties of low molecular weight heparins, their simpler (fixed) dosing regimens, and few or no laboratory monitoring requirements, low molecular weight heparins are gradually replacing heparin for the initial treatment of most patients diagnosed with acute pulmonary embolism, except in very obese patients or patients with renal failure. Only selected patients with massive, life-threatening pulmonary embolism should be managed with intravenously administered thrombolytic drugs, surgical embolectomy, or catheter-based embolectomy. Likewise, inferior vena caval filter should be considered only in patients with an absolute contraindication to, or a documented failure of, anticoagulant therapy. New anticoagulants, such as ximelagatran, an oral direct thrombin inhibitor, or fondaparinux and idraparinux, selective factor X(a) inhibitors with an almost complete bioavailability after subcutaneous injection are promising alternatives, but these drugs have yet to find a place in the initial treatment of pulmonary embolism in standard day-to-day clinical practice. Long-term anticoagulation treatment is still provided by antivitamin K antagonists (eg, warfarin), which unfortunately have a narrow therapeutic window. Consequently, time-consuming monitoring is required to ensure the therapeutic anticoagulant effect. A target International Normalized Ratio (INR) of 2.5 (INR range: 2.0 to 3.0) is recommended for warfarin therapy. This treatment should be continued for at least 3 months for patients with a first episode of pulmonary embolism secondary to a transient (reversible) risk factor, or up to 6 to 12 months for patients with a first episode of idiopathic pulmonary embolism.

Interventional bronchoscopy for treatment of tracheal obstruction secondary to benign or malignant thyroid disease.

STUDY OBJECTIVES: Surgery is the treatment of choice for symptomatic tracheal obstruction due to benign or malignant thyroid disease. In case of inoperability, or when surgery is refused, few therapeutic alternatives are available. Interventional bronchoscopic procedures have only been reported anecdotally. The objective of this study is to evaluate the results of interventional bronchoscopic procedures in the treatment of severe tracheal obstruction due to thyroid disease. STUDY DESIGN: Retrospective cohort analysis. SETTING: University hospital, tertiary referral center. PATIENTS: Thirty consecutive patients referred for bronchoscopic treatment of benign (n = 17) or malignant (n = 13) thyroid-related upper airway obstruction due to tracheomalacia, extrinsic compression, and/or tracheal ingrowth. Indications for bronchoscopic treatment were medical or surgical inoperability, prevention or treatment of tracheomalacia, and refusal of surgery. There were no procedure-related complications. INTERVENTIONS: Rigid bronchoscopy with dilatation, stenting and/or Nd-YAG laser treatment, and clinical follow-up. MEASUREMENTS AND RESULTS: Subjective improvement, pulmonary function tests, early and late complications, and survival. In the benign group, immediate (100% relief of dyspnea) and long-term (88% relief of dyspnea) results were excellent after airway stenting (21 stents used in 17 patients). There was one unrelated death 1 week after stenting in a 98-year-old patient. There were 6% and 30% short-term and long-term complications, respectively, that could be managed endoscopically. In the malignant group, Nd-YAG laser treatment (n = 3) and stenting (n = 13) yielded immediate and long-term success in 92% of patients. There were 15% short-term and 8% long-term complications. Median survival time was 540 days. CONCLUSIONS: Interventional bronchoscopic procedures including Nd-YAG laser treatment and stenting are valuable alternatives to surgery in inoperable thyroid-induced tracheal obstruction, or when surgery is refused.

Detecting upper airway obstruction in patients with tracheal stenosis.

We propose a forced oscillation test modality for detecting upper airway obstruction (UAO) as an alternative to spirometric UAO indices in patients with tracheal stenosis. From oscillometry performed at different breathing flow rates, airway resistance at 5 Hz was determined at 0.5 l/s (R), and flow dependence of resistance was computed as the regression slope of resistance vs. flow up to 1 l/s (Delta R/Delta V). It was first verified by measurement in 10 normal subjects and 10 patients with chronic obstructive pulmonary disease that Delta R/Delta V was unaffected by the presence of peripheral airway obstruction and that external orifices (with lumen area down to 28 mm(2)) induced marked increases in R and Delta R/Delta V. Ten patients eligible for tracheal dilatation underwent spirometry and impulse oscillometry before and after intervention. Considering the lumen area of tracheal stenosis in the patients (42 +/- 28 mm(2), represented as the mean +/- SD), the R and Delta R/Delta V increases were of similar magnitude to those predicted by the external orifices. In addition, R (r = -0.68; P = 0.001) and Delta R/Delta V (r = -0.65; P = 0.001) showed better correlations with minimal tracheal lumen than any spirometric UAO index. Delta R/Delta V, but not R, showed a consistent return to normal after intervention in the stenosis patients. We conclude that the forced oscillation test at different breathing flow rates up to 1 l/s provides a measure of UAO, namely flow dependence of resistance Delta R/Delta V, which can signal a critical level of tracheal stenosis and is not confounded by the presence of concomitant peripheral airway obstruction.

Use of likelihood ratios improves interpretation of laboratory testing for pulmonary sarcoidosis.

Laboratory tests for pulmonary sarcoidosis (percentage lymphocytes and CD4/CD8 ratio in bronchoalveolar lavage fluid and serum angiotensin-converting enzyme activity) lack sensitivity and specificity. In a retrospective study of 153 subjects under suspicion of pulmonary sarcoidosis (36 cases and 117 patients with other diseases [control patients]), we defined likelihood ratios (LRs) for rationally selected result intervals of these tests, which improve clinical interpretation as compared with dichotomous interpretation based on a single cutoff value. By using logistic regression analysis, we further integrated the 3 individual tests into a unified algorithm that could rule out diagnosis in 57 (48.7%) of the 177 control subjects and confirm diagnosis in 12 (33%) of the 36 pulmonary sarcoidosis cases. We conclude that use of LRs improves interpretation of laboratory tests for pulmonary sarcoidosis. In addition, we present a prediction algorithm based on the combination of laboratory tests that helps clinicians confirm or exclude diagnosis in almost half of the study population.

Genetic variation in three candidate genes and nicotine dependence, withdrawal and smoking cessation in hospitalized patients.

AIMS: This study evaluates the relationship of six polymorphisms found in the CHRNA3, DRD2 and COMT genes with nicotine dependence, the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients. MATERIALS & METHODS: The study included 233 participants from a double-blind, placebo-controlled trial of nicotine patch substitution with a 6-month follow-up period. Nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND) questionnaire, withdrawal symptoms by the Minnesota Nicotine Withdrawal Scale questionnaire and smoking cessation by self-reported abstinence at 1 week, 1 month and 6 months after treatment. RESULTS: After correcting for multiple testing, three polymorphisms in the DRD2 gene (Taq1A, Taq1B and Pro319Pro) were significantly associated with nicotine dependence (p = 0.018, p = 0.048 and p = 0.006, respectively). Using a cutoff point for the FTND score, the CHRNA3 Tyr215Tyr (rs1051730) polymorphism was also associated with nicotine dependence (p = 0.037 and p = 0.074 after correction for multiple testing). No association of any of the studied polymorphisms was observed with either smoking cessation or the occurrence of withdrawal symptoms. CONCLUSION: This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence.

Final overall results of a study with a novel triplet induction chemotherapy regimen (PACCAGE) followed by consolidation radiotherapy in locally advanced inoperable non-small cell lung cancer (NSCLC).

INTRODUCTION: We report the long term and overall results of a triplet induction chemotherapy regimen followed by standard radiotherapy in patients with locally advanced inoperable stage III non-small cell lung cancer. METHODS: Three cycles of paclitaxel, carboplatin, and gemcitabine were administered every 3 weeks before standard fractionated consolidation radiotherapy starting at least 4 weeks after the last chemotherapy administration. Toxicity and antitumor response was assessed in detail as well as the progression free and overall survival. RESULTS: Sixty-four patients (25 stage IIIA and 39 stage IIIB) received a total of 179 cycles of chemotherapy. Fifty-six received the planned three cycles. Full-dose radiotherapy was administered in 47 patients (73%), a reduced dose in 11 (17%) and none in six (10%). A 55% objective response rate (OR) (one complete and 34 partial responses) was observed after induction chemotherapy. After completing the whole treatment including radiotherapy, the OR was 40 of 47 evaluable patients (85%). Median time to progression was 10.9 month and median overall survival was 17.2 month, with a significant difference between stage IIIA and stage IIIB patients (23.4 versus 10.5 month; p = 0.011). The strongest predictor for a favorable long-term outcome was a metabolic complete response after chemotherapy. CONCLUSION: Induction chemotherapy with the paclitaxel, carboplatin, and gemcitabine regimen preceding radiotherapy in patients with locally advanced inoperable stage III non-small cell lung cancer was feasible and active. Radiotherapy could be administered at a full dose in the majority of patients with acceptable toxicity. Long-term survival results of this sequential chemoradiotherapy regimen appear similar to those of concurrent treatment. Patients not achieving a metabolic complete response after induction chemotherapy should be the focus of studies aiming at improved local control.

Small airway function improvement after smoking cessation in smokers without airway obstruction.

OBJECTIVE: Studying smokers with normal spirometry requires monitoring tools of the peripheral lung. A validated multiple breath washout technique was used to assess possible recovery of smoking-induced small airway malfunction in acinar and conductive lung zones. METHODS: Eighty-seven smokers with a smoking history of at least 10 pack-years but absence of spirometric airflow obstruction were invited for assessment of lung function and small airway function at baseline and after 1 wk, 3 mo, 6 mo, and 12 mo of smoking cessation. A control group of 16 persistent smokers was studied at the same time intervals. MEASUREMENTS AND MAIN RESULTS: Of the 87 smokers, 66, 32, 28, and 21% successfully ceased smoking for 1 wk, 3 mo, 6 mo, and 12 mo, respectively. Lung function parameters remained essentially unaffected by smoking cessation. Ventilation heterogeneity showed transient improvements after 1 wk in the acinar lung compartment with a return to baseline afterwards. By contrast, there were persistent improvements in the conductive airway compartment; for example, smokers who successfully quit smoking for 12 mo (n=18) showed a 30 and 42% reduction of conductive airways abnormality after 1 wk and 1 yr, respectively. CONCLUSIONS: Smokers with early signs of small airway malfunction who successfully quit smoking show sustained improvements of conductive airway malfunction. In contrast, acinar airway malfunction quickly returns to baseline after a transient improvement.

Percutaneous placement of marking coils before stereotactic radiation therapy of malignant lung lesions.

PURPOSE: To evaluate a technique for implantation of radiopaque markers in lung nodules as an aid in extracranial stereotactic radiation therapy. MATERIALS AND METHODS: An implantation technique was developed for marking intrapulmonary lung lesions by introducing a vascular coil through a coaxial needle in or near the target tumor. The markers were placed percutaneously through 15- or 20-gauge coaxial needles in 41 lesions (25 patients) under computed tomographic fluoroscopic guidance. Two different types of vascular helical coils where used. RESULTS: All lesions were accessible for puncture and coils could be placed in all lesions. Four types of complications were observed, some as a result of the learning curve in the technique: (i) coil misplacement subcutaneously (5%); (ii) small needle trajectory bleeding in the lung (10%); (iii) pneumothorax, for which one patient (10%) in whom the coil was placed through a 15-gauge coaxial needle needed chest tube drainage and required hospitalization; and (iv) one subcutaneous metastasis probably unrelated to the puncture (2.5%). CONCLUSION: With this technique, lung nodules can be marked with radiopaque implants in a safe and accurate way.

Noninvasive assessment of airway alterations in smokers: the small airways revisited.

It has been shown that structural changes in small airways of smokers with average smoking histories greater than 35 pack-years could be reflected in the single-breath washout test. The more sophisticated multiple breath washout test (MBW) has the potential to anatomically locate the affected small airways in acinar and conductive lung zones through increased phase III slope indices S(acin) and S(cond), respectively. Pulmonary function, S(acin), and S(cond) were obtained in 63 normal never-smokers and in 169 smokers classified according to smoking history (< 10 pack-years; 10-20 pack-years; 20-30 pack-years; > 30 pack-years). Compared with never-smokers, significant changes in S(acin) (p = 0.02), S(cond) (p < 0.001), and diffusing capacity (DL(CO); p < 0.001) were detected from greater than 10 pack-years onwards. Spirometric abnormality was significant only from greater than 20 pack-years onwards. In smokers with greater than 30 pack-years and DL(CO) less than 60% predicted, the presence of emphysema resulted in disproportionally larger S(acin) than S(cond) increases. We conclude that S(cond) and S(acin) can noninvasively detect airway changes from as early as 10 pack-years onwards, locating the earliest manifestations of smoking-induced small airways alterations around the acinar entrance. In these early stages, the associated DL(CO) decrease may be a reflection of ventilation heterogeneity rather than true parenchymal destruction. In more advanced stages of smoking-induced lung disease, differential patterns of S(acin) and S(cond) are characteristic of the presence of parenchymal destruction in addition to peripheral airways alterations.

Fluorescein-enhanced autofluorescence thoracoscopy in primary spontaneous pneumothorax.

The exact site of air leakage in a patient with primary spontaneous pneumothorax is difficult to determine and locate. In particular, the role of rupture of emphysema-like changes (blebs and bullae) versus that of enhanced porosity of lung parenchyma in the pathophysiology of primary spontaneous pneumothorax remains unclear. This is the first description of a patient with recurrent primary spontaneous pneumothorax in whom inhalation of aerosolized fluorescein followed by autofluorescence thoracoscopy allowed in vivo localization of various lung areas of extensive subpleural fluorescein accumulation which were not, or only partly, visibly abnormal during normal white light thoracoscopy. No air leak was present at the time of thoracoscopy. No emphysema-like changes were seen. Our findings suggest substantial areas of parenchymal abnormality that remain unnoticed by white light thoracoscopic inspection of the parenchymal surface. In this respect, fluorescein-enhanced autofluorescence thoracoscopy may become an exciting tool in the study of the pathophysiology of primary spontaneous pneumothorax, and could prove useful in clinical practice in determining the sites of surgical staple resection whenever this treatment modality is considered.