Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial.

BACKGROUND: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. METHODS: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. RESULTS: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. CONCLUSION: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.

Hypersensitivity to chemotherapeutics: a cross sectional study with 35 desensitisations.

BACKGROUND: Chemotherapy is one of the main treatments for lung cancer, and in these patients, discontinuation of treatment due to uncontrollable hypersensitivity reactions (HSRs) is an important problem. AIM: To determine the frequency of HSRs during chemotherapy and to review current approaches. METHODS: We did a cross sectional study in patients undergoing chemotherapy for lung cancer in a reference chemotherapy unit from January 2012 to January 2013. Patients who developed immediate-HSRs or delayed-HSRs to chemotherapeutics and gave consent were included into study. The effectiveness of a standardised 12-step "rapid drug desensitisation" (RDD) procedure was investigated in patients with immediate-HSRs. RESULTS: In total, 1,099 cycles of chemotherapy were administered to 292 patients in 1 year. We observed ten HSRs, during ten cycles in ten patients (~3 % of the patients). Two HSRs were delayed-type, eight were immediate-type at grade 1-3. Of those with immediate-type HSR, five patients with grade 2-3, and additional two referred patients with grade 4 HSRs were successfully given their culprit drug in 35 cycles of chemotherapy with 12-step or modified 20-step RDD protocol. CONCLUSIONS: HSRs to chemotherapeutics are not so rare. Premedication alone does not prevent such reactions. The results of RDD treatment look promising for continuing treatment with the culprit chemotherapeutic agent.

New-Onset Hypercalcemia After Renal Transplant: An Infectious Etiology Beyond Persistent Hyperparathyroidism.

Pneumocystis jirovecii pneumonia is an opportunistic infection in kidney transplant recipients. It may be complicated by hypercalcemia. Here, we discuss a 59-year-old man who presented with respiratory symptoms and hypercalcemia. He had undergone a deceased donor kidney transplant 2 years previously. The patient had persistent hyperparathyroidism, but his serum calcium level was normal. At the time of admission, his serum calcium level had increased and his parathyroid hormone level was suppressed. He was diagnosed with Pneumocystis jirovecii pneumonia. Serum calcium and parathyroid hormone levels returned to baseline values after treatment. Pneumocystis jirovecii pneumonia is an important infection that can present with hypercalcemia among kidney transplant recipients.

Beta-2 agonist discussions in asthma and a review of current data.

Current guidelines recommend inhaled steroids as the first line control medication in the treatment of asthma. However, many patients particularly with airway obstruction need bronchodilators either as a symptom reliever or control medication to provide relaxation of bronchiolar smooth muscles. Both short acting and long acting beta-2 agonists (SABA and LABA) are of particular importance among the bronchodilators used in asthma. Despite their well-known benefits, in the recent years, a growing body of publications has been published on the safety of LABAs. However, the increased risk reported to be related to LABA monotherapy was not observed in patients receiving inhaled corticosteroid as the standard treatment in combination with LABA. The benefits of adding LABAs to inhaled corticosteroid have been thoroughly documented, while the risks, including asthma mortality, are currently under debate. Pharmacogenetic advancements drew attention to a potential genetic explanation for certain side effects of these medications whose efficacy and safety have been proven in several studies. In conclusion, LABAs are effective in relieving symptoms and improving lung functions and safe when combined with inhaled corticosteroid in asthma; however, LABA monotherapy should never be administered in the absence of inhaled corticosteroid treatment. Asthma patients that lack control of disease despite adequate doses of inhaled corticosteroids need addition of a regular bronchodilator to their treatment regimen.

Prevalence of gastroesophageal reflux disease in patients with asthma and chronic obstructive pulmonary disease.

BACKGROUND AND AIM: It is speculated that the prevalence of gastroesophageal reflux disease (GERD) might increase with asthma or chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the prevalence of GERD in patients with asthma and COPD in an area representative of developing countries. METHODS: A validated GERD questionnaire was conducted face-to-face with 308 consecutive asthma (240 women) and 133 COPD (35 women) patients in the tertiary referral pulmonary outpatient clinic, and 694 controls from the research area. Detailed histories of patients and pulmonary function tests were also recorded. RESULTS: The prevalence of GERD (heartburn/regurgitation once a week or more) was 25.4%, 17.0%, 19.4% and occasional symptoms (less than weekly) were 21.2%, 16.3% and 27.0% of patients with asthma, COPD and controls, respectively. The prevalence was higher in the asthma group compared with the controls and the COPD group. No significant difference was found between the COPD group and the controls. Heartburn started following pulmonary disease in 24.1% of the asthma group, and 26.4% of the COPD group. The majority of additional symptoms were significantly higher in asthmatics compared with the controls. No difference was found in the consumption of pulmonary medications in asthmatic patients in groups with different symptom frequency. Heartburn was increased 13.8% by the consumption of inhaler medications. CONCLUSIONS: These results implicate that the prevalence of GERD in asthma and COPD are lower than in published reports in a tertiary referral center. These differences might be related to the characteristics of developing countries, increased consumption of powerful medications in GERD and pulmonary diseases, or methodological flaws in earlier studies.

COVID-19 Pandemic and the Global Perspective of Turkish Thoracic Society.

It has been more than 3 months now since the first case of COVID-19 was reported in Turkey. Globally, the number of confirmed cases and deaths reached 9,653,048 and 491,128 respectively, as reported by 216 countries by June 27, 2020. Turkey had 1,396 new cases, 194,511 total cases, and 5,065 deaths by the same date. From the first case until today, the Turkish Thoracic Society (TTS) has been very proactive in educating doctors, increasing public awareness, undertaking academic studies, and assisting with public health policies. In the present report, social, academic, and management perspectives of the pandemic are presented under appropriate subtitles. During this critical public health crisis, TTS has once again demonstrated its readiness and constructive stance by supporting public health, healthcare workers, and the environment. This review summarizes the perspective of TTS on each aspect of the COVID-19 pandemic and casts light on its contributions.

Electromyography-Guided Botulinum Toxin Injection Into the Cricothyroid Muscles in Bilateral Vocal Fold Abductor Paralysis.

OBJECTIVES: Bilateral vocal fold abductor paralysis (BVFAP) both deteriorates quality of life and may cause life-threatening respiratory problems. The aim of this study was to reduce respiratory symptoms in BVFAP patients using cricothyroid (CT) botulinum toxin (BTX) injection. METHODS: Before and 2 weeks and 4 months after bilateral BTX injection into the CT muscles under electromyography; alterations in respiratory, acoustic, aerodynamic and quality of life parameters were evaluated in BVFAP patients with respiratory distress. For the respiratory evaluation modified Borg scale and spirometry, for the voice and aerodynamic evaluations Voice Handicap Index-30 (VHI-30), GRBAS, acoustic analysis (sound pressure level, F0, jitter%, shimmer%, noise-to-harmonic ratio) and maximum phonation time and for the quality of life assessment Short Form-36 (SF-36) form were used. RESULTS: All patients were female with a mean age of 47±8.1 years. There was a mean time of 11.8±5.5 (minimum 2, maximum 23) months between BVFAP development and BTX injection. In all cases, other than one case with unknown aetiology, the cause of vocal fold paralysis was prior thyroid surgery. In total 18.6±3.1 units of BTX were applied to the CTs. In the preinjection period, and the 2nd week and 4th month after injection, the Borg dyspnea scale was 7.3/5.3/5.0, FIV1 (forced inspiratory volume in one second) was 1.7/1.7/1.8 L, peak expiratory flow (PEF) was 1.4/1.7/2.1 L/sec, maximum phonation time was 7.0/6.4/6.2 seconds and VHI-30 was 63.2/52.2/61.7 respectively. There was no significant alteration in acoustic analysis parameters. Many of the patients reported transient dysphagia within the first week. There were insignificant increases in SF-36 sub-scale values. CONCLUSION: After BTX injection, improvements in the mean Borg score, PEF and FIV1 values and SF-36 sub-scale scores showed the restricted success of this approach. This modality may be kept in mind as a transient treatment option for patients refused persistent tracheotomy or ablative airway surgeries.

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens. METHODS: A total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy. RESULTS: Patients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups (P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils). CONCLUSIONS: Our results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity.

[Clinical features and diagnostic approach to sarcoidosis according to stages]. / Sarkoidozda Evrelere Göre Klinik Ozellikler ve Tanisal Yaklasim.

Seventy-seven patients with sarcoidosis followed in our department evaluated retrospectively and the study continued prospectively. Depending on the radiologic findings, 26 (33.8%) of these cases were considered to be in stage 1, 47 (61.0%) were in stage 2 and 4 (5.2%) were in stage 3. Erythema nodosum was found in 29 (37.7%) cases; 15 (51.7%) of whom were stage 1, 13 (44.8%) were stage 2 and 1 (3.4%) was stage 3. There was peripheral lymphadenopathy in 8 (10.4%) cases. Bronchoscopy was performed in 68 cases and 55 found to be normal. BAL was determined in 50 of those to whom bronchoscopy had been performed. Mean BAL lymphocyte rate was found to be 32.2% and it was 36.1% in stage 1, 31.1% in stage 2 and 22.2% in stage 3. Diagnosis of sarcoidosis was confirmed with histopathologic examination in 48 cases and with BAL and other clinical signs in the others. It was confirmed with parenchymal biopsy in 15 cases, with scalene lymph node biopsy in 8 cases, with bronchial mucosa biopsy in 5, with transcranial needle aspiration biopsy in 5, with video-assisted thoracoscopic surgery in 4, with right supraclavicular lymph node biopsy in 3 and with skin biopsy in 2 cases. Tuberculin skin test was performed in 67 cases and was found to be negative in 51 (76.1%). Serum ACE levels were checked in 11 cases and found to be high in 7 of them (63.6%) (mean: 21.9). Two of 55 cases who had neurologic examination, 3 of 60 cases who had fundoscopy were found to have pathologic findings.

Respiratory impairment due to asbestos exposure in brake-lining workers.

There is extensive evidence that exposure to asbestos causes pulmonary parenchymal fibrosis, pleural disease, and malignant neoplasm in asbestos-exposed workers. However, few data concerning brake-lining workers are available in the literature. In this study, we aimed to assess the long-term effects of chrysotile asbestos exposure on lung function and the risk of asbestos-related diseases in brake-lining workers. Seventy-four asbestos-exposed workers who processed brake-lining products and 12 unexposed office workers were offered pulmonary function tests (spirometry and transfer factor) in 1992 and 1999. In 1999, the mean duration of asbestos exposure was 10.00+/-4.07 and 11.02+/-4.81 years (7-31 years) in nonsmoking and smoking asbestos workers, respectively. Transfer factor (T(L), CO) and transfer coefficient (K(CO)) decline were significant in the 7-year follow-up in both smoking and nonsmoking asbestos workers. However, lung function indices of the control group, whom were all current smokers; were also found to be decreased, including FEF(75), T(L), CO and K(CO). We found minimal reticular changes in 10 asbestos workers who were all current smokers, they underwent high-resolution computed tomography scans of the chest and we found that they had peribronchial thickening resulting from smoking. As a conclusion, even in the absence of radiographic asbestosis, T(L), CO and K(CO) may decrease after a mean 10-year duration of exposure to asbestos in brake-lining workers and this is more noticeable with cigarette burden.

The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis and bronchial hyperresponsiveness (BHR) may be at higher risk of developing asthma. OBJECTIVE: To investigate whether reactivity to aeroallergens in skin prick testing (SPT) and serum eosinophil cationic protein levels can be used to predict BHR in allergic rhinitis patients. METHODS: Fifty-nine consecutive patients with allergic rhinitis underwent SPTs using grass, tree, weed, parietaria, Alternaria, Aspergillus, mites, and cat and dog dander extracts. Methacholine challenge tests were performed using spirometry. RESULTS: Methacholine-induced BHR was detected in 23 patients (39%). Of 59 patients, 14 had 1 positive SPT response, 35 had 2 to 4 positive responses, and 10 had more than 4 positive responses. There was a significant inverse correlation between methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) and the number of positive SPT responses (r = -0.28; P = .03). The BHR-positive patients had a mean of 4 positive SPT responses, whereas BHR-negative patients had a mean of 2.6 (P = .04). Nine BHR-positive patients (39%) and only 1 BHR-negative patient (3%) had more than 4 positive SPT responses (P < .001). There was no correlation between serum eosinophil cationic protein levels and methacholine PC20 doses. There was a strong association between hyperresponsiveness to methacholine and both cat and dog dander sensitivity (P < .001 and P = .001, respectively). CONCLUSIONS: Allergic rhinitis patients with SPT responses to a higher number of allergens are more likely to have BHR. Whether the number of positive SPT responses correlates with the risk of developing asthma in allergic rhinitis patients remains to be determined.