Anikó Bohács

Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.

Background: Both lung transplant recipients and candidates are characterised by reduced training capacity and low average quality of life (QoL). This review investigates the impact of training on exercise ability and QoL in patients before and after lung transplant. Methods: Searches were conducted from the beginning to 7 March 2022 using the terms “exercise,” “rehabilitation,” “lung transplant,” “exercise ability,” “survival,” “quality of life” and “telerehabilitation” in six databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, CINAHL, Nursing and Allied Health, and Scopus. The inclusion criteria were studies evaluating the effects of an exercise training programme concurrent with lung transplantation as well as patients and candidates (>18 years old) through any lung diseases. The term “lung transplant rehabilitation” was used to refer to all carefully thought-out physical activities with the ultimate or intermediate objective of improving or maintaining physical health. Results: Out of 1422 articles, 10 clinical- and 3 telerehabilitation studies, candidates (n = 420) and recipients (n = 116) were related to the criteria and included in this review. The main outcome significantly improved in all studies. The 6-min walk distance, maximum exercise capacity, peak oxygen uptake, or endurance for constant load rate cycling improved measuring physical activity [aerobic exercises, breathing training, and aerobic and inspiratory muscle training sessions (IMT)]. Overall scores for dyspnoea improved after exercise training. Furthermore, health-related quality of life (HRQOL) also improved after aerobic exercise training, which was performed unsupervised or accompanied by breathing sessions. Aerobic training alone rather than combined with inspiratory muscle- (IMT) or breathing training enhanced exercise capacity. Conclusion: In conclusion, rehabilitation programmes seem to be beneficial to patients both preceding and following lung transplantation. More studies are required to determine the best training settings in terms of time scale, frequency, and work intensity in terms of improving exercise ability, dyspnoea, and HRQOL.

Introduction: Lung transplant recipients (LuTX) represent a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Even though many vaccines are already developed, more clinical data need to support effective immunological response in immunocompromised patients.Methods: Stable LuTX recipients with no medical history of coronavirus disease (COVID‐19) were enrolled. Currently available messenger RNA (mRNA) (BNT162b2‐mRNA, mRNA‐1273) and non‐mRNA (ChAdOx1, BBIBP‐CorV) vaccines were given according to availability, boosters were all mRNA‐based. SARS‐CoV‐2 Spike1 immunoglobulin G (IgG) antibody titer was evaluated before and 2 weeks after second and third dose. Difference between mRNA versus non‐mRNA vaccines was assessed.RESULTS: Forty‐one patients (49% men, age 48.4 ± 13.8 years) received two doses of SARS‐CoV‐2 vaccines: 23 of mRNA, 18 of non‐mRNA, and 24/41 (58%) received a third dose. Median 92 months passed since transplantation, and serum level of tacrolimus was median 5.5 ng/ml. Positive serology was found in 37% of all patients after the second dose, 86% had mRNA vaccine. After the third dose, 29% became positive who had no antibody before. Significantly higher level of antibody was found after the second mRNA than non‐mRNA vaccines (2.2 vs. 1568.8 U/ml, respectively, p = .002). 6/23 (26%) patients received two doses of mRNA vaccine developed COVID‐19 after the second injection in an average of 178 days, half of them recovered, half of them died in intensive care unit (ICU). 3/6 (50%) patients with two doses mRNA and recovered from COVID‐19 had significantly higher level of antibody (average 20847.3 U/ml) than without infection. After the booster vaccine, 1/24 (4%) developed infection.Conclusion: Immunosuppression therapy may induce a weaker SARS‐CoV‐2 response in LuTX recipients; therefore, third dose is a priority in transplanted patients. The highest antibody level was measured recovering from COVID after two doses. Our data confirm that booster mRNA vaccine could increase antibody levels, even if immunization was started with non‐mRNA vaccine.

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included (n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud’s phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m²) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged.

Soluble urokinase-type plasminogen activator receptor (suPAR) is upregulated by inflammation and plays a role in the pathogenesis of atherosclerosis. Chronic obstructive pulmonary disease (COPD) is associated with enhanced systemic inflammation and increased risk for atherosclerosis, however, studies analysing the circulating suPAR levels in COPD are contradictory. The aim of the study was to investigate plasma suPAR concentrations together with markers of arterial stiffness in COPD.

Background: After lung transplantation (LuTX) a high level of immunosuppression is needed to prevent rejection of the graft. Together with earlier colonization by pathogens, immunosuppression makes recipients more susceptible to infections, especially during the first postoperative year. As seasonality of lower respiratory tract infections (LRTI) is well‐known in chronic lung diseases, we assessed seasonal changes of pathogen spectrum and number of infections in the first postoperative year in LuTX recipients.Methods: LRTI were analyzed in 28 Hungarian adult LuTX patients. Incidence and spectrum of microorganism causing LRTI were evaluated according to post‐transplant time and seasonal temperature and humidity changes.Results: A total of 69 cases of LRTI were registered (average: 1.9 cases/patient; range: 0‐14). Gram‐negative=59, gram‐positive=26, and fungal=31 pathogens were detected, with polymicrobial samples in 46% of all cases. Increased number of LRTI was observed in the cold season (1.68±1.54 vs 0.79±0.92 case/month/patient, P<.01) and significant negative correlations were identified between the incidence of polymicrobial and bacterial infections and temperature (r²=0.1535, P<.05, r²=0.3144, P<.01, respectively). In addition, positive correlation was observed between polymicrobial infections and humidity (r²=0.1403, P<.05). Higher incidence of LRTI was also noted in the cold season, when accounting for the differences in immunosuppression.Conclusion: Seasons influenced the incidence of LRTI in the first postoperative year in LuTX recipients. More intensive vigilance for possible gram‐negative and polymicrobial infections is needed in these patients in cold and wet seasons in the continental climate zone, regardless of underlying disease.

Background: The immunosuppressive treatment after organ transplantation highly contribute to evolve cardiovascular comorbidities like hypertension, hyperlipidemia, diabetes and kidney diseases. The effect of hypertriglyceridemia could cause accelerated atherosclerosis. Previous smoking and excessive inflammatory response could increase the cardiovascular risk on those patients who were transplanted because of end-staged chronic obstructive pulmonary disease. Long term follow up needed on lung transplanted (LuTx) patient with cardiovascular risk assessment and to screen patients with vulnerable cardiovascular diseases. However, the correlation between LuTx patients and arterial stiffness is not investigated in the literature. Method: We investigated the arterial stiffness parameters in 51 LuTx and 49 healthy individuals. The arterial stiffness parameters were measured with oscillometric method (Tensiomed Arteriograph). Aortic pulse wave velocity (aoPWV), augmentation index (Aix), central systolic blood pressure (cSBP) and aortic pulse wave reflection time (RT) were determined. Results: We found increased aoPWV and Aix values in lung transplanted (LuTx) patients than in the healthy individuals. Significant higher aoPWV (8.45 vs 7.49 m/s; p = 0.045), and RT (120 vs 134 ms; p = 0,0004) were found. Patients who were transplanted because of COPD and lung fibrosis the aoPWV were significantly higher versus the patient who were transplanted because of cystic fibrosis or pulmonary hypertension. Conclusion: We strongly recommend the long term cardiovascular follow up on lung transplanted patient, because of the common systemic atherogen effect of the frequent infection and immunsupressive therapy.

Objective: Asthma often complicates pregnancy and represents a risk for complications. Periostin is considered as a biomarker of asthma; however, as it also plays a role in normal gestation, pregnancy may influence circulating periostin levels. This is the first study assessing periostin in asthmatic pregnancy. Methods: Plasma periostin levels were investigated in asthma (asthmatic non-pregnant, ANP; N = 19) and asthmatic pregnancy (AP; N = 14), compared to healthy non-pregnant controls (HNP; N = 12) and healthy pregnant women (HP; N = 17). The relationship between periostin levels and asthma control determinants was also evaluated. The diagnostic efficacy of periostin to detect uncontrolled asthma was analyzed using ROC analysis. Results: Plasma periostin levels were similar in the HNP and ANP (55.68 [37.21–67.20] vs. 45.25 [32.67–64.55], p > 0.05), and elevated in the HP (68.81 [57.34–98.84] ng/mL, p = 0.02 vs. HNP) and AP groups (54.02 [44.30–74.94] ng/mL, p = 0.0346 vs. ANP). Periostin levels of the two pregnant groups were similar (p > 0.05). In AP women periostin correlated negatively with FEV₁ (r = −0.5516) and positively with Raw (r = 0.5535; both p < 0.05). Conclusions: Pregnancy itself increases circulating periostin levels and this elevation is detectable in asthmatic pregnancy as well. Although periostin correlates with lung function in asthmatic pregnancy, periostin as a biomarker has to be handled with caution in pregnant patients due to the influence of pregnancy on its plasma level.

BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant ( n = 21) and healthy pregnant women ( n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576–2.563), 1.783 (IQR 0.6064–2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively ( P = .02 in all cases). C5a correlated negatively with FEV ₁ (r = −0.44, P = .039) and FVC values (r = −0.64, P = .001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the non-pregnant asthma group ( n = 12, r = 0.78, P = .004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] μg/mL vs 559.7 [IQR 388.7–783.1] μg/mL, P = .002 and P = .004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] μg/mL, P = .10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma).