Tiotropium in Patients with Bronchiectasis: A Prospective Cohort Study

Purpose

There are limited studies on the use of bronchodilators for the treatment of bronchiectasis. This study investigated the efficacy of tiotropium in patients with bronchiectasis and airflow limitation.

Methods

This study was a prospective cohort study, including 169 patients with bronchiectasis and airflow limitation from 2015 to 2019. The clinical outcomes observed in our study were the effect of tiotropium on the frequency of moderate exacerbations, the time to the first severe exacerbation, and the annual decline in FEV₁.

Results

After 12 months, the annual decline in the FEV₁ after bronchodilator use was 27.08 ml or 42.9 ml per year in the group with or without tiotropium, respectively. Treatment with tiotropium was associated with a decreased risk of moderate exacerbation of bronchiectasis (Adjusted RR 0.618 95% CI 0.493–0.774; P?<?0.005). The time to the first severe acute exacerbation of bronchiectasis in the tiotropium group was longer than the non-tiotropium group (Adjusted HR 0.333 95% CI 0.219–0.506; P?<?0.001).

Conclusion

In conclusion, prospective cohort study showed that tiotropium effectively ameliorated the annual decline in the FEV_1, with a lower-risk rate of moderate exacerbations and prolonging the time to the first-time severe exacerbation in patients with bronchiectasis and airflow limitation.

     

Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes

Abstract. Fyhrquist F, Tiitu A, Saijonmaa O, Forsblom C, Groop P‐H, on behalf of the FinnDiane Study Group (Minerva Institute for Medical Research; Helsinki University Central Hospital; and Folkhälsan Institute of Genetics; Helsinki, Finland). Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes. J Intern Med 2010; 267 : 278–286. Objectives. To determine whether short telomere length of blood leucocytes from patients with type 1 diabetes is associated with or predictive of progression of diabetic nephropathy. Design and methods. Two consecutive DNA samples were obtained from 132 patients from the nationwide Finnish Diabetic Nephropathy Study with type 1 diabetes. Control DNA samples were taken from 44 healthy blood donors. Telomere length was measured by Southern blot. Patients were divided into three groups according to their urinary albumin excretion rate (AER): 48 patients with normoalbuminuria (AER < 20 μg min^?1); seven patients with microalbuminuria (AER ≥ 20 μg min^?1 <200 μg min^?1) and 77 patients with macroalbuminuria (AER ≥ 200 μg min^?1). Progression was defined as a change in albuminuria to a higher level. Results. Progression occurred in 21 patients. Progressors had shorter mean telomere length (8.1 ± 0.7 kb, mean ± SD; P = 0.017) and higher percentage of short telomeres (32.0 ± 8%, P = 0.002) than nonprogressors (8.5 ± 0.7 kb and 27 ± 7.2%, respectively). Thus, both shorter telomeres (HR = 0.190, 95%CI 0.065–0.558, P = 0.0025) and higher proportion of short telomeres (HR = 1.115, 1.039–1.195, P =0.0023) were independent predictors of diabetic nephropathy. Telomere length was not associated with the degree of albuminuria and was not different in patients with type 1 diabetes compared with healthy controls. Conclusions. Short telomeres are independent predictors of progression of diabetic nephropathy in patients with type 1 diabetes.     

Down-expression of Foxj1 on airway epithelium with impaired cilia architecture in non-cystic fibrosis bronchiectasis implies disease severity

Introduction

The pathogenesis of non-cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non-cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity.

Methods

Lung tissue sections excised from 47 patients with non-cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1.

Results

Of the 47 patients with non-cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non-cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non-cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) μm versus (7.34 ± 0.71) μm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 10⁶ in non-cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 10⁶ in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity.

Conclusion

Foxj1 declined in the airway epithelium of patients with non-cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity.     

High Flow Nasal Therapy Use in Patients with Acute Exacerbation of COPD and Bronchiectasis: A Feasibility Study

Abstract

The efficacy and feasibility of high flow nasal therapy (HFNT) use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and bronchiectasis is unknown. We performed a single-center, single-arm prospective observational study in patients with AECOPD, documented bronchiectasis, pH ≥ 7.35, respiratory rate (RR) ≥ 26 breaths/minute despite receiving maximal medical treatment and oxygen via face mask up to 10?L/m. Patients received HFNT (Airvo 2, Fisher & Paykel) at a gas flow of 50?L/min and FIO₂ adjusted to maintain SpO₂ ≥92%. Dyspnea, rated by Borg scale, RR, arterial blood gases and mucus production (ranging from 1 to 3) were collected before and 1?h after starting HFNT and then every 24?h for 3?days. Tolerance was measured using a visual analogic scale (VAS). Fifteen patients were enrolled. After 24?h, patients showed a significant improvement in dyspnea score [Borg scale from 6.7?±?1.4 to 4.1?±?1.3 (p<.001)]; RR decreased from 29.6?±?2.7?breaths/min to 23.2?±?2.9?breaths/min (p<.001); pCO2 significantly decreased after 24?h [58.4?±?13 vs. 51.7?±?8.2 (p=.003)] while quantity of mucus production increased [(1.1?±?0,6 vs. 2.4?±?0.7, p<.001)]. No patient received invasive or noninvasive mechanical ventilation. Overall VAS score for HFNT tolerance was 6.5. HFNT was effective in improving dyspnea score, decreasing RR, improving gas exchange, and increasing mucus production in patients with AECOPD and coexisting bronchiectasis. Moreover, no safety concerns on its use were detected. Nevertheless, due to the single-arm design, the effect of HFNT could not be isolated from standard pharmacological treatment due to the study design.     

COPD-related Bronchiectasis; Independent Impact on Disease Course and Outcomes

Background: COPD and radiographic bronchiectasis frequently coexist but the effect of this on the clinical course of COPD is not fully understood. We determined the impact of bronchiectasis on clinical outcomes in COPD patients, independent of coexisting emphysema and bronchial wall thickening (BWT). Methods: COPD patients admitted with first exacerbation 1998–2008 were identified retrospectively using ICD10 codes J44.0,1,8,9. Patients with suitable CT scans were graded for severity of bronchiectasis, emphysema and BWT on a 5 point scale (0-absent, 1-minor, 2-mild, 3-moderate, 4-severe). Results: 406 patients (71 ± 11 years, 56% male, FEV₁ 52 ± 23% predicted) were included; 278 (69%) patients had bronchiectasis: minor, 112 (40%); mild, 81 (29%); moderate, 62 (22%); severe 23 (8%). Bronchiectasis severity correlated with severity of BWT (p < 0.001) but not emphysema (p = 0.090). Bronchiectasis independently determined sputum isolation of Pseudomonas aeruginosa (Odds ratio (OR) 1.39 (95% CI 1.07 to 1.80), p = 0.013) and atypical mycobacteria (OR 2.44 (95% CI 1.04 to 5.69), p = 0.040), annual respiratory admissions (p = 0.044) and inpatient days (p < 0.001), but did not predict survival (p = 0.256). Conclusions: Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore an important diagnosis with potential implications for treatment.     

Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.     

Mucoactive agents for chronic,non‐cystic fibrosis lung disease: A systematic review and meta‐analysis

Inhaled mucoactive agents are used in respiratory disease to improve mucus properties and enhance secretion clearance. The effect of mannitol, recombinant human deoxyribonuclease/dornase alfa (rhDNase) and hypertonic saline (HS) or normal saline (NS) are not well described in chronic lung conditions other than cystic fibrosis (CF). The aim of this review was to determine the benefit and safety of inhaled mucoactive agents outside of CF. We searched Medline, Embase, CINAHL and CENTRAL for randomized controlled trials investigating the effects of mucoactive agents on lung function, adverse events (AEs), health‐related quality of life (HRQOL), hospitalization, length of stay, exacerbations, sputum clearance and inflammation. There were detrimental effects of rhDNase in bronchiectasis, with average declines of 1.9–4.3% in forced expiratory volume in 1 s (FEV₁ ) and 3.7–5.4% in forced vital capacity (FVC) (n = 410, two studies), and increased exacerbation risk (relative risk = 1.35, 95% CI = 1.01–1.79 n = 349, one study). Some participants exhibited a reduction in FEV₁ (≥10–15%) with mucoactive agents on screening (mannitol = 158 of 1051 participants, rhDNase = 2 of 30, HS = 3 of 80). Most AEs were mild and transient, including bronchospasm, cough and breathlessness. NS eased symptomatic burden in COPD, while NS and HS improved spirometry, HRQOL and sputum burden in non‐CF bronchiectasis. Mannitol improved mucociliary clearance in asthma and bronchiectasis, while the effects of N‐acetylcysteine were unclear. In chronic lung diseases outside CF, there are small benefits of mannitol, NS and HS. Adverse effects of rhDNase suggest this should not be administered in non‐CF bronchiectasis.     

Brief Report: Shortened Telomere Length in Patients With Systemic Lupus Erythematosus

Objective

Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length.

Methods

Telomere length was measured cross‐sectionally in whole blood from SLE patients and age‐matched healthy female controls, using real‐time quantitative polymerase chain reaction. SLE‐related and cardiovascular risk factors were assessed.

Results

We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37–59 years) and 49.9 years (IQR 32–60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47–1.57), compared to 1.53 (IQR 0.82–2.29) in controls (P = 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (β ± SE −0.36 ± 0.16; P = 0.023), and longer telomere length was associated with steroid therapy (0.29 ± 0.14; P = 0.046). We also noted an association of longer telomere length with increasing body mass index (β ± SE 0.07 ± 0.01; P < 0.0001) and tobacco smoking (0.64 ± 0.26; P = 0.016), as well as with the presence of carotid plaque (0.203 ± 0.177; P = 0.032).

Conclusion

Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.

     

Long-term follow-up of recipients of allogeneic bone marrow grafts reveals no progressive telomere shortening and provides no evidence for haematopoietic stem cell exhaustion

Summary. Accelerated telomere shortening has been proposed as a possible long‐term risk of allogeneic bone marrow transplantation (allo‐BMT). In this study we monitored telomere length in white blood cells (WBC), granulocytes, and naïve and memory CD4⁺ T lymphocytes in recipients of allo‐BMT at long‐term follow‐up. Peripheral blood was collected from 10 allo‐BMT recipients and donors at a median interval of 18 years after allo‐BMT. Telomere length was determined using Southern blot analysis. Similar to results previously reported at short‐term follow‐up, a small difference in telomere length (0·1–0·3 kb) between recipients and donors was detected in WBC, granulocytes and naïve CD4⁺ T cells. Our data therefore provide no evidence for sustained telomere shortening in leucocytes, and render the possibility of long‐term haematopoietic graft failure unlikely. In addition, we observed two phenomena that may be related to involution of the thymus. First, the number of naïve CD4⁺ T cells in the blood was significantly lower in recipients (0·4 × 10⁹/l) than in donors (0·7 × 10⁹/l) (P < 0·05). Second, telomeres in memory CD4⁺ T cells from recipients were on average 0·6 kb shorter than those from donors (P = 0·01). The latter may be related to the reported rapid peripheral expansion of memory T cells immediately after transplantation.     

Mycobacterium avium-intracellulare Pulmonary Infection in Patients Without Known Predisposing Lung Disease

We tried to characterize the clinical features and findings on chest high resolution computed tomography (HRCT) of patients with Mycobacterium avium-intracellulare (MAI) pulmonary infection without known predisposing lung disease and with no immunodeficiency. We also aimed to clarify the small airway and alveolar inflammation using bronchoalveolar lavage (BAL) from the affected regions. MAI infection was diagnosed in 53 patients from respiratory samples, including sputum and materials obtained using a fiberoptic bronchoscope. None had a predisposing lung disease or immunodeficiency, as assessed by medical history, routine laboratory data, and previously normal chest radiographs and/or CT scans. The mean age of the 53 patients was 60 ± 11 years, and 48 were nonsmoking females. They had few respiratory symptoms, although 42% had chronic paranasal sinusitis. Chest HRCT findings showed centrilobular small nodules and ectasia of small bronchi and/or bronchioles located mainly in segment (S) 2, 3, 4, and 5. S1, which is usually affected by pulmonary tuberculosis, was completely free of these opacities. The BAL study revealed that the predominant cells were activated T lymphocytes and neutrophils. The CD4⁺/CD8⁺ ratio increased significantly. Bacteriology was negative for other bacteria and fungi. Although our patients did not present with distinct respiratory symptoms, the regions affected by MAI showed a chronic inflammation of mainly neutrophils and activated T lymphocytes. The presence of chronic sinusitis may be merely coincidental. However, its high prevalence and the finding of bronchiectasis in chest HRCT raise the question of whether silent bronchiectasis may be a predisposition. Accepted for publication: 18 June 1998     

Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients

Introduction. Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. Methods. This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23–86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient’s leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2–42) months. Results. Telomere length was shorter in CKD men, despite women being older (average ± SD 6.41 ± 1.23 vs. 6.96 ± 1.48 kb, P = 0.002). Telomere length was associated with age (rho = −0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = −0.21, P = 0.005) and IL-6 (rho = −0.17, P = 0.02). In a multivariate logistic regression (pseudo r² = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels. Conclusion. Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.     

Genetic risk factors for serious infections in inflammatory bowel diseases

Introduction: Immunosuppression, the cornerstone of management of Crohn’s disease (CD) and ulcerative colitis (UC) (inflammatory bowel diseases; IBD) is associated with an increased risk of serious infections that is inadequately predicted by clinical risk factors. The role of genetics in determining susceptibility to infections is unknown.

Methods: From a prospective-consented patient registry, we identified IBD patients with serious infections requiring hospitalization. Analysis was performed to identify IBD-related and non-IBD related immune response loci on the Immunochip that were associated with serious infections and a genetic risk score (GRS) representing the cumulative burden of the identified single nucleotide polymorphisms was calculated. Multivariable logistic regression used to identify effect of clinical and genetic factors.

Results: The study included 1333 IBD patients (795?CD, 538 UC) with median disease duration of 13 years. A total of 133 patients (10%) had a serious infection requiring hospitalization. Patients with infections were more likely to have CD and had shorter disease duration. The most common infections were skin and soft-tissue, respiratory and urinary tract infections. Eight IBD risk loci and two other polymorphisms were significantly associations with serious infections. Each one point increase in the infection GRS was associated with a 50% increase in risk of infections (OR?=?1.53, 95% CI?=?1.37–1.70) (p?=?1?×?10^?14), confirmed on multivariable analysis. Genetic risk factors improved performance of a model predicting infections over clinical covariates alone (p?<?0.001).

Conclusions: Genetic risk factors may predict susceptibility to infections in patients with IBD.     

Immune senescence and cancer in elderly patients: Results from an exploratory study

Background

The challenge of immune senescence has never been addressed in elderly cancer patients. This study compares the thymic output and peripheral blood telomere length in ≥ 70 year old cancer patients.

Patients and methods

Fifty-two elderly cancer patients and 39 age-matched controls without personal history of cancer were enrolled. All patients underwent a Comprehensive Geriatric Assessment (CGA), from which a multidimensional prognostic index (MPI) score was calculated. Peripheral blood samples were studied for naïve and recent thymic emigrant (RTE) CD4⁺ and CD8⁺ cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels, telomere length and telomerase activity in peripheral blood cells were quantified by real-time PCR.

Results

The percentages of CD8⁺ naïve and CD8⁺ RTE cells and TREC levels were significantly lower in cancer patients than in controls (p = 0.003, p = 0.004, p = 0.031, respectively). Telomere lengths in peripheral blood cells were significantly shorter in cancer patients than in controls (p = 0.046) and did not correlate with age in patients, whereas it did in controls (r = − 0.354, p = 0.031). Short telomere (≤ median)/low TREC (≤ median) profile was associated with higher risk of cancer (OR = 3.68 [95% CI 1.22–11.11]; p = 0.021). Neither unfitness on CGA nor MPI score were significantly related to thymic output or telomere length in either group.

Conclusions

Immune senescence is significantly worse in elderly cancer patients than in age-matched controls. The low thymic output and the shorter telomeres in peripheral blood cells of cancer patients may reflect a pre-existing condition which facilitates the onset of malignancies in elderly people.     

Persistent sputum cellularity and neutrophils may predict bronchiectasis

BACKGROUND:

Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.

OBJECTIVE:

To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.

METHODS:

A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details.

RESULTS:

The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×10⁶/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity.

CONCLUSIONS:

Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.     

Elevated level of circulating CD4+Helios+FoxP3+ cells in primary Sjogren’s syndrome patients

Objective: This study was designed to investigate the expression of regulatory T cells in primary Sjögren’s Syndrome (pSS) and to evaluate the clinical role of CD4?⁺?Helios⁺?FoxP3⁺ cells in pSS patients.

Methods: CD4?⁺?FoxP3^+?T cells in the peripheral blood of 39 pSS patients and 30 healthy controls were measured by flow cytometry and CD25 and Helios expression were also analyzed. The repression ability of CD4?⁺?CD25^hi cells was tested in vitro. Clinical information of pSS patients was retrospectively collected and their correlations with circulating Treg cells were analyzed. Cytokine levels in plasma were measured by ELISA and correlations with Helios⁺?FoxP3^+?cells were also detected.

Results: Circulating FoxP3^+?and Helios⁺?FoxP3^+?cells were elevated in pSS patients compared with controls. The suppression function of CD4?⁺?CD25^hi cells is not different between two groups. There are inverse correlations between Helios⁺?FoxP3^+?percentage and ESR, IgG, IgM and ESSDAI. Anti-SSB^? patients possess higher level of Helios⁺?FoxP3^+?cells than anti-SSB^+?patients. IL-6, IFNγ and IFNα levels were increased in pSS plasma and there were positive correlations between the levels of IFNγ/IFNα and percentage of Helios⁺?FoxP3^+?cells.

Conclusion: Circulating Helios ⁺?FoxP3⁺ cells were elevated in pSS patients and may contribute to suppressing autoimmunity in pSS patients.     

Culturally Appropriate Outreach Specialist Respiratory Medical Care Improves the Lung Function of Children in Regional and Remote Queensland

Background and Objectives

Indigenous Respiratory Outreach Care (IROC) is a culturally appropriate specialist respiratory service established to deliver multidisciplinary respiratory care to regional and remote Queensland communities. Our objective was to evaluate the impact of an outreach specialist respiratory service on the spirometry of children attending IROC clinics, particularly Indigenous children with asthma and bronchiectasis.

Methods

Retrospective single-arm cohort study of 189 children who performed spirometry at twelve sites across regional and remote Queensland between October 2010 and December 2017. Each child’s baseline spirometry was compared to their best spirometry at follow-up visit occurring within (1) 12 months of their most recent visit with at least 12 months of specialist care and; (2) each year of their first 3 years of care.

Results

Forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) z-scores improved significantly across the whole group from baseline to follow-up (change in z-scores (Δz) of FEV₁ = 0.38, 95% CI 0.22, 0.53; ΔzFVC = 0.36, 95% CI 0.21, 0.51). In subgroup analyses, lung function significantly improved in Indigenous children (n = 141, ΔzFEV₁ = 0.37, 95% CI 0.17, 0.57; ΔzFVC = 0.36, 95% CI 0.17, 0.55) including those with asthma (n = 117, ΔzFEV₁ = 0.41, 95% CI 0.19, 0.64; ΔzFVC = 0.46, 95% CI 0.24, 0.68) and bronchiectasis (n = 38, ΔzFEV₁ = 0.33, 95% CI 0.07, 0.59; ΔzFVC = 0.26, 95% CI − 0.03, 0.53). Significant improvements in FEV₁ and FVC were observed within the first and second year of follow-up for Indigenous children, but not for non-Indigenous children.

Conclusion

The IROC model of care in regional and remote settings leads to significant lung function improvement in Indigenous children with asthma and bronchiectasis.

     

The clinical significance of a shortened activated partial thromboplastin time in patients with connective tissue disease

Introduction

Connective tissue disease (CTD) patients have been reported to have an increased risk of venous thromboembolism (VTE). Deep venous thrombosis represents a potential emergency that may have a fatal outcome. The D-dimer test is the most widely accepted screening marker for VTE; however, elevation of the plasma D-dimer level without demonstrable thrombosis sometimes accompanies CTD activity itself, infection, and other conditions. Thus, the accuracy of a diagnosis of VTE based on a D-dimer test result is lower in CTD patients. The activated partial thromboplastin time (APTT) test is a very common and simple test.

Method

The medical records of 535 CTD patients were retrospectively investigated. The following data were extracted: APTT, D-dimer, thrombotic events, laboratory data, and systemic corticosteroid therapy.

Results

The rates of thrombotic events and VTE were significantly increased in patients with a shortened APTT (<?26 s) (PSAPTT) in comparison to those without a shortened APTT (p?=?0.004, 0.0009, respectively). The number of PSAPTTs was significantly increased in patients with VTE in comparison to those without VTE (p?=?0.0009). In the diagnosis of VTE in CTD patients, the specificity and positive predictive value (PPV) of the D-dimer test were 71.6% and 83.8% and 12.7% and 19.4%, respectively. The combination of a shortened APTT and elevated plasma D-dimer level improved the specificity and PPV to 94.7% and 97.3% and to 25.0% and 36.4%, respectively.

Conclusions

For the evaluation of possibility of accompanying VTE in CTD patients, APTT shortened was useful and should be evaluated with careful attention.

Key Points

? Regarding the specificity for diagnosing VTE in CTD patients, a shortened APTT showed a value (84.3%) comparable or superior to that of the D-dimer test.

? The combination of a shortened APTT and elevated D-dimer level improved the specificity of the diagnosis of VTE in CTD patients to (94.7% or 97.3%) in comparison to the D-dimer test alone (71.6% or 83.8%).

? The positive predictive value of the combination of a shortened APTT and plasma D-dimer elevation for the diagnosis of VTE in CTD patients increased to 25.0% or 36.4%.

? In the management of CTD patients, physicians should pay attention when they encounter patients with a shortened APTT, as it may indicate VTE.

     

Telomere length changes in patients undergoing hematopoietic stem cell transplantation.

Telomere length indicates the replicative history of cells, serving as a molecular measure of the replicative potential remaining in cells. To investigate telomere length changes in hematopoietic stem cells, patients undergoing hematopoietic stem cell transplantation (HSCT) were evaluated. Fifteen patients after allogeneic bone marrow transplantation (allo-BMT group), seven patients after autologous peripheral blood stem cell transplantation (auto-PBSCT group), and 39 healthy controls were studied. Telomere length was measured in peripheral mononuclear cells by Southern blot hybridization. There was no significant difference between the allo-BMT and the auto-PBSCT groups. In the allo-BMT group, the mean telomere length of recipients was 2.01 kb shorter than that of their donors (P = 0. 008), and was 1.59 kb shorter than that of age-matched putative normal controls (P = 0.002). Telomere shortening in the allo-BMT group was equivalent to 41.4 years of aging in the donors, and to 52. 4 years of aging in the normal controls. The mean telomere length in the auto-PBSCT group was 2.36 kb shorter than that of the age-matched putative controls (P = 0.043), which was equivalent to 61.5 years of aging in normal controls. The extent of telomere shortening in the allo-BMT group showed a trend to negative correlation with the number of mononuclear cells infused. These findings suggest that hematopoietic stem cells after HSCT lose telomere length and these shortened telomeres may result in a higher incidence of clonal disorders later in life.     

Premature telomere shortening in polymorphonuclear neutrophils from patients with systemic lupus erythematosus is related to the lupus disease activity

We investigated whether premature telomeric loss occurred in peripheral polymorphonuclear neutrophils (PMN) as well as mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE). We measured the telomere length of MNC and PMN in 60 SLE patients and 26 sex-, race- and age-matched healthy volunteers by Southern blotting with chemiluminescence method. The possible predisposing factors associated with telomere change were also analysed. We found the telomere length of MNC and PMN shortened with age in different degrees in both SLE and control groups. Compared to the control group, the telomere length was shortened in both SLE-MNC (6.08 kb in SLE versus 6.71 kb in control, P = 0.0008) and PMN (6.24 kb in SLE versus 6.75 kb in control, P = 0.0025). The average reduction in telomere length in SLE patients was equivalent to a premature senescence of 16.5 years in MNC and 13.4 years in PMN. In addition, the accelerated telomere shortening was more prominent in SLE patients younger than 45 years old. SLE disease activity (SLEDAI) contributed remarkably to the accelerated telomere erosion, at least in PMN. Moreover, the telomere length of MNC was significantly shorter than PMN in the same SLE patients with leukopenia and lymphopenia. These data suggested that MNC and PMN from patients with SLE displayed premature and accelerated telomere shortening that SLE is an independent factor for it.