Treatment outcomes and long-term survival of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in a real-world setting are difficult to assess, especially for species other than Mycobacterium avium complex (MAC).This was a retrospective cohort study on all Croatian residents with respiratory NTM isolates from 2006 to 2015, with follow-up to 2020.Therapy was started in 98/137 (71.5%) of patients, significantly more often in patients with fibrocavitary disease and/or sputum smear positivity. Unsuccessful treatment outcomes were recorded in 39/98 (39.8%) patients (14 deaths and 25 treatment failures). One-year and 5-year all-cause mortality were respectively 18.2% and 37.6%. Guideline-based treatment (GBT) was started in 50/98 (51%) of treated patients and followed for the recommended duration in 35.7% (35/98). This resulted in a higher chance of cure (OR 3.79, 95% CI 1.29 to 11.1; P = 0.012) than inadequately treated/untreated patients. For Mycobacterium xenopi disease, high cure rates (>80%) were achieved both with GBT and non-GBT treatment regimens.Guideline-based therapy resulted in a four-time higher chance of being cured. The impact of GBT on treatment outcomes was clear for MAC disease, but no apparent effect was observed for patients with M. xenopi disease.

Introduction: HFNC is currently used in various settings and could provide optimal respiratory support for most bronchoscopic procedures including EBUS TBNA. Primary objective: to describe the efficacy, complication rate and risk factors for desaturation when using HFNC during EBUS TBNA. Methods: prospective, observational, single center study. All patients eligible for EBUS TBNA in deep sedation (RASS -4) during the 2 year study period were supported by HFNC (FiO2 0.5, flow rate 60L/min). Desaturation was defined as a persistent drop of SpO2 <88% requiring further intervention. Results: A total of 362 patients underwent EBUS TBNA, 41.4% female and 58.6% male, with a mean age of 63.5 years. HFNC provided effective respiratory support in 343 (95.7%) cases. Desaturation occurred in 5.3% (19/362) of cases requiring laryngeal mask insertion in 12 and endotracheal intubation in 7 patients. The average BMI in the whole cohort, stable (SG) and desaturation group (DG) were 27.0, 26.8 and 29.7 with 63.5%, 57.4% and 84.2% of patients having above normal BMI, respectively. There were 21.3% (73/343) obese patients in the SG, and 47.4% (9/19) in the DG (p=0.02). Respiratory insufficiency (RI) prior to EBUS was noted in 29.6% (107/362) of total cases, 28.6% (98/343) in the SD and 47.7% (9/19) in the DG (p=0.12). Serious adverse events included 1 cardiac arrest with successful resuscitation, transient hemodynamic instability in 7, vomiting in 3 and bronchospasm in 1 case. Unexpected ICU admission was required for 3 patients. Conclusion: HFNC provides adequate respiratory support during EBUS for most patients. However, desaturation was significantly more frequent among obese patients.

BACKGROUND: The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are limited. RESEARCH QUESTION: Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline? STUDY DESIGN AND METHODS: We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 degrees C, 5mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe). RESULTS: Atotal of 2,033 FBswere performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline armand 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 +/- 1.3 [n = 1.8 +/- 0.8]; TXA: mean VAS score, 5.3 +/- 1.4 [n = 1.8 +/- 0.8]). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P =.008 and P =.012, respectively) and required more applications for severe bleeding (3.0 +/- 0 and 2.4 +/- 0.5, respectively) than moderate bleeding (1.7 +/- 0.8 and 1.7 +/- 0.8, respectively) control (P =.006 and P =.002, respectively). We observed no drug-related adverse events in either group. INTERPRETATION: We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB.

Major challenges in the identification of non-tuberculous mycobacteria (NTM) by MALDI-TOF MS include protein extraction protocol and updating of the NTM database. The aim of this study was to evaluate MALDI Biotyper Mycobacteria Library v6.0 (Bruker Daltonics GmbH, Bremen, Germany) for identification of clinical NTM isolates and its impact on clinical management. NTM isolates cultivated from clinical samples in 101 patients were identified simultaneously by PCR-reverse hybridization (Hain Lifescience GmbH, Nehren, Germany) as a routinely used reference molecular method and using MALDI Biotyper Microflex LT/SH after protein extraction. Each isolate was applied to eight spots, and mean scores were used in analysis. MALDI-TOF MS obtained correct identification to the species level for 95 (94.06%) NTM isolates. The majority of correctly identified isolates (92/95; 96.84%) were identified with high-confidence score of ≥1.80 and only 3.16% (3/95) with a score of <1.80. Mean value ± SD of RGM NTM isolates (2.127 ± 0.172) was statistically significant higher in comparison to SGM NTM isolates (2.027 ± 0.142) with a p value of 0.007. In comparison to PCR-reverse hybridization, discordant identification results by MALDI-TOF MS were found in six (6/101; 5.94%) NTM isolates for which clinical data were analyzed. We demonstrated a high confidence NTM identifications using Mycobacterium Library v 6.0 on routine clinical isolates. This is the first study that analyzed MALDI-TOF MS identification results of NTM isolates in the context of clinical data, and it showed that MALDI-TOF MS with its updated databases could help clarify the epidemiology, clinical characteristics, and course of infections caused by less frequent NTM species.

Introduction: Hypersensitivity pneumonitis (HP) is an ILD characterized by a complex immunological reaction of the lung parenchyma in response to repetitive inhalation of a sensitized allergen. Patients with HP and presence of fibrosis have worse outcome. Aim and objectives: To evaluate tretment response and the annual change in lung function tests in patients with fibrotic and non-fibrotic HP. Methods: In this retrospective, observational study, data were collected from patients treated in our Clinic during the last 10 years. We analyzed demographic, radiological findings, the annual rate of lung function change (FVC, DLCO) during the therapy, and threatment approach. Results: We included 83 patients; 47 females and 36 males; 49 patients had fibrotic, and 34 had non-fibrotic HP. Among patients with non-fibrotic HP, 85% patients were treated only with glucocorticoids versus 40% patients in fibrotic group. In non-fibrotic group 6% patients were treated with steroid sparing agents versus 57% patients in fibrotic group. After 1 year of treatment in fibrotic group 61% patients had significant decline of FVC and 48.9% of DLCO while in non-fibrotic HP FVC declined in 38.2% and DLCO in 26.5% patients. Improvement of FVC (for 8%) was observed in 39% patients from fibrotic group and in 43% patients of DLCO (for 9%) while in non-fibrotic group significant increase of FVC (for 17%) was observed in 59% and of DLCO (for 18%) in 68% patients. Conclusion: Glucocorticoids were treatment option for most of the patients with HP. Despite the more agressive treatment approach most patients with fibrotic HP had greater decline in FVC and DLCO and further treatment options are needed.

Tracheal complications should be suspected in mechanically ventilated COVID-19 survivors with respiratory symptoms. Treatment requires a multimodal approach of interventional bronchoscopy and surgery with tight follow-up due to a high rate of restenosis. https://bit.ly/3iw05xQ.

Introduction: The most commonly used topical haemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on usage of other agents such as tranexamic acid (TXA) for this purpose are limited. Aims and objectives: to compare the efficacy of topical TXA versus adrenaline in controlling iatrogenic bleeding during FB. Methods: we conducted a cluster-randomized, double blind, single centre trial in a tertiary teaching hospital. Following haemostasis failure after 3 applications of cold saline (4°C, 5ml), patients were randomized to receive up to 3 applications of TXA (100mg, 2ml) or adrenaline (0.2mg, 2ml). If bleeding persisted, crossover was allowed (for up to 3 further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analogue scale (VAS; 1 - very mild, 10 - severe). Results: 2033 FB were performed during the study period with 563 bleeding episodes (mean VAS 2,82 ± 1,4). Bleeding was stopped with cold saline in 432 patients (76.7%). 130 patients were randomized to adrenaline (N=65) or TXA (N= 65). There were no differences in bleeding control rate between the groups - bleeding was stopped in 83.1% (54/65) and 83.1% (54/65) patients receiving adrenaline or TXA, respectively (p=1). The severity of bleeding and number of applications needed for bleeding control (N) were similar in both groups (adrenaline mean VAS = 4,94 ± 1,31, N=1.78 ± 0.79; TA mean VAS = 5,25 ± 1,44, N= 1.78 ± 0.79). Conclusion: The majority of bleeding during FB was successfully stopped with cold saline. TXA was not inferior to adrenaline in controlling moderately severe endobronchial bleeding.

Lung transplantation is a therapeutic option for the treatment of advanced lung disease. The risk of pulmonary infections is increased in lung transplant recipients. We report a case of a pulmonary coinfection with Mycobacterium tuberculosis and Nocardia species in a lung transplant recipient.

Introduction: Postintubation tracheal stenosis (PITS) is a rare complication of mechanical ventilation (MV). Risk factors for PITS include prolonged MV, reintubation and poor endotracheal tube cuff management, all of which are common in severe COVID19 patients during pandemic surges. Aims and objectives: to describe the patient characteristics and outcomes of PITS after MV for COVID19. Methods: we conducted a retrospective review of all patients referred to our tertiary teaching hospital for endoscopic PITS treatment after COVID19 during 2021. Results: 60% of the 15 referred patients were female with a mean age of 60.1 years. Median duration of MV was 11.5 (8.5 – 16) days. 13.3% of patients were reintubated and 26.7% required tracheostomy during their ICU stay. 86.7% presented with stridor after a median of 32 (16.5-60) days after extubation with a further delay of 14 (2-42) days until the diagnosis of PITS. 73.3% had simple PITS with a mean diameter of 5.73±1.53 mm. 12 patients were successfully treated endoscopically with serial dilatation and electrocautery. Restenosis after treatment was observed in 66.7% of patients after a median of 30 (22.5-35) days. 5 patients required surgery while 2 patients required further endoscopic dilatation after surgery. Interestingly, 13 of the 15 patients were referred from a single tertiary hospital, after treatment in the same ICU. Conclusions: We observed an increase in referrals for PITS treatment during the study period with a cluster of patients from a single ICU. The high restenosis rate emphasizes the importance of multidisciplinary management as well as the prevention of PITS with high quality ICU care during the COVID19 pandemic.

Anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers (approximately 5%) what gives patients better survival outcomes. We analyzed the data of the patients diagnosed with advanced stage ALK positive NSCLC in University hospital center Zagreb, Department for pulmonary diseases from January 2018 until December 2020. In observed period of time 64 patients were treated with ALK TKIs. 29 patients were treated with crizotinib in the first line and 27 of them progressed at the time of data cut off and 25 received alectinib in the second line, while one patient was treated with brigatinib. 35 patients were treated with alectinib in the first line. In the third line setting 10 patients were treated with brigatinib or lorlatinib. ALK TKIs were administered in the first line setting in 44 patients, in the second line setting in 14 patients and some patients were treated in the third, fourth and even fifth line (2, 3 and 1, respectively). There were 35 (55%) females with median age of 65 years (36-82). Almost half of them (43%) were current or ex-smokers with median pack/years 26.9 (2-75). Diagnosis was established by cytology specimens in 18 (27%) and by histology specimens in 46 (73%) patients. We observed median overall survival for all treated patients (mOS) of 47 months (95%CI 21.6-72.3), while mOS for patients treated with alectinib in the first line was not reached. Median progression-free survival (mPFS) was 12 months (95%CI 6,2 -14,7), but divided by TKIs - for crizotinib was 8 months (95% CI 5,1 – 10,8) and for alectinib it was not reached. mPFS2 for alectinib is 12 months (95%CI 2,3 – 21,6). We present real-life data of survival outcomes associated with sequencing of different ALK TKIs. Our data suggest that treatment with alectinib in the first line gives better survival benefit than earlier generation ALK TKIs.

BACKGROUND:To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic.SUBJECTS AND METHODS:We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status.RESULTS:An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable.CONCLUSION:Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.

Lung cancer is one of the most common cancer type[JM1] s in both genders, resulting in most of cancer-related deaths every year Since there are no data on the five-year survival of patients in Croatia, the aim of our research was to present real-life data for the first time.

The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. We conducted a retrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was a significant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

This study evaluated the prevalence of spreading pathways in nontuberculous mycobacteria (NTM) pulmonary infections according to nodular distribution patterns seen on chest computed tomography (CT). This study included 63 patients diagnosed with NTM lung infections who underwent CT at our institution. A retrospective analysis of CT images focused on the presence and distribution of nodules, presence of intrathoracic lymphadenopathy and the predominant side of infection in the lungs. The findings were classified into five groups; centrilobular (bronchogenic spread), perilymphatic (lymphangitic spread), random (hematogenous spread), combined pattern and no nodules present. The groups were then compared according to other CT findings. Among 51 (81%) patients identified with a nodular pattern on chest CT, 25 (39.8%) presented with centrilobular, 7 (11.1%) with perilymphatic, 6 (9.5%) with random and 13 (20.6%) with combined nodular patterns but located in different areas of the lungs. The right side of the lungs was predominant in 38 cases (60.3%). Intrathoracic lymphadenopathy was evident in 20 patients (31.7%). Significant differences in distributions of nodular patterns were seen in patients infected with Mycoplasma avium complex (MAC) associated with centrilobular pattern (p = 0.0019) and M. fortuitum associated with random pattern (p = 0.0004). Some of the findings were related to perilymphatic nodules between other isolated species of NTM (p = 0.0379). The results of this study showed a high proportion of perilymphatic nodules and right-sided predominance in the upper lobe, which, combined with intrathoracic lymphadenopathy is highly suggestive of the lymphangitic spread of lung NTM infections.