Publications by authors named "Natalie Lorent"

28 Publications

  • Page 1 of 1

COVID-19 recovery: benefits of multidisciplinary respiratory rehabilitation.

BMJ Open Respir Res 2021 09;8(1)

Department of Respiratory Diseases, KU Leuven University Hospitals Leuven, Leuven, Belgium.

Many patients struggle with ongoing symptoms in different domains (physical, mental, cognitive) after hospitalisation for COVID-19, calling out for a multidisciplinary approach. An outpatient multidisciplinary rehabilitation programme, according to a respiratory rehabilitation strategy, was set up for adult patients who were able to attend group sessions during 12 weeks. Results of 22 adult patients with COVID-19, of which 15 had required intensive care, were analysed and some general impressions and challenges of rehabilitation in COVID-19 were reported. Impressive results on physical recovery were determined after 6 weeks and 3 months, with significant improvement of lung function, muscle force and exercise capacity variables. A positive evolution of mental and cognitive burden was present, although less pronounced than the physical recovery. These mental and cognitive consequences seem, next to musculoskeletal and medical complications, the most challenging aspect of rehabilitating patients with COVID-19. These real-world data show feasibility and efficiency of a multidisciplinary respiratory rehabilitation programme after moderate to severe COVID-19 disease.
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http://dx.doi.org/10.1136/bmjresp-2020-000837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423511PMC
September 2021

The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia.

Int J Mol Sci 2021 Jun 8;22(12). Epub 2021 Jun 8.

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium.

The airways of patients with primary ciliary dyskinesia (PCD) contain persistently elevated neutrophil numbers and CXCL8 levels. Despite their abundance, neutrophils fail to clear the airways from bacterial infections. We investigated whether neutrophil functions are altered in patients with PCD. Neutrophils from patients and healthy controls (HC) were isolated from peripheral blood and exposed to various bacterial stimuli or cytokines. Neutrophils from patients with PCD were less responsive to low levels of fMLF in three different chemotaxis assays ( < 0.05), but expression of the fMLF receptors was unaltered. PCD neutrophils showed normal phagocytic function and expression of adhesion molecules. However, PCD neutrophils produced less reactive oxygen species upon stimulation with bacterial products or cytokines compared to HC neutrophils ( < 0.05). Finally, the capacity to release DNA, as observed during neutrophil extracellular trap formation, seemed to be reduced in patients with PCD compared to HC ( = 0.066). These results suggest that peripheral blood neutrophils from patients with PCD, in contrast to those of patients with cystic fibrosis or COPD, do not show features of over-activation, neither on baseline nor after stimulation. If these findings extend to lung-resident neutrophils, the reduced neutrophil activity could possibly contribute to the recurrent respiratory infections in patients with PCD.
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http://dx.doi.org/10.3390/ijms22126172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230338PMC
June 2021

Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization.

Semin Thromb Hemost 2021 Jun 23;47(4):362-371. Epub 2021 Apr 23.

Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium.

Background:  Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis.

Methods:  Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation-perfusion (V/Q) scan to screen for incidental pulmonary embolism.

Results:  Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported.

Conclusion:  In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.
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http://dx.doi.org/10.1055/s-0041-1727284DOI Listing
June 2021

Impact of COVID-19: urging a need for multi-domain assessment of COVID-19 inpatients.

Eur Geriatr Med 2021 08 30;12(4):741-748. Epub 2021 Mar 30.

Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.

Objective: To retrospectively analyse data obtained from the multi-domain assessment of hospitalized COVID-19 patients, to describe their health status at discharge, and to investigate whether subgroups of patients, more specific ICU patients and older adults (> 70 years), had more (or less) risk to experience specific impairments.

Methods: Retrospective case series in the University Hospitals Leuven, Belgium of confirmed COVID-19 patients 'after surviving an ICU-stay', 'aged ≥ 70 years', or 'aged < 70 years with a length of hospitalization > 7 days'. Exclusion criteria were 'unwilling to cooperate', 'medically unstable', or 'palliative care policy'. Following tests were used: 'Five Times Sit To Stand Test', 'hand grip dynamometry', 'Barthel index', 'Swallowing screening', 'Montreal Cognitive Assessment', 'Hospital Anxiety and Depression Scale', and 'Nutritional Risk Screening 2002'.

Results: One or more tests were obtained in 135/163 patients (83.3%). Physical impairments were present in 43.2-82.8% of the patients. Median BI was 10/20 indicating limited self-dependency. Swallow impairments were present in 3/53 (5.7%) and 24/76 (31.6%) had risk of malnutrition. Impaired memory was seen in 26/43 (60.5%) and 22/47 (46.8%) had elevated anxiety/depression scores. Older adults had more physical, functional, and cognitive impairments. ICU patients had a lower hand grip force.

Conclusion(s): The high prevalence of physical, cognitive, psychological, and functional impairments in hospitalized COVID-19 patients, both ICU and non-ICU patients, indicates that assessment of impairments is imperative. These results imply that rehabilitation and follow-up is essential for these patients. This paper proposes a short, workable assessment composed with known outcome measures to assess different domains of COVID-19 patients.
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http://dx.doi.org/10.1007/s41999-021-00486-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009466PMC
August 2021

Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection.

J Clin Virol 2021 03 18;136:104765. Epub 2021 Feb 18.

Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

Background: Most SARS-CoV-2 infected patients develop IgG antibodies within 2-3 weeks after symptom onset. Antibody levels have been shown to gradually decrease in the first months after infection, but few data are available at six months or later.

Methods: A retrospective multi-center study was performed using 652 samples of 236 PCR-confirmed SARS-CoV-2 infected patients from 2 Belgian University hospitals. Patients were included if at least two samples were available (range 2-7 samples); including at least one sample collected 30 days or later after first positive PCR (range 0-240 days). Of those 236 patients, 19.1 % were classified as mild/asymptomatic (mild) and 80.9 % as moderate to critical (severe). IgG anti-nucleocapsid antibodies (anti-N) were measured using the Abbott Architect immunoassay.

Results: 22.2 % of mild and 2.6 % of severe COVID-19 cases never seroconverted (p < 0.001). Of the mild patients who seroconverted 0-59 days after PCR; 18.8 %, 40.0 % and 61.1 % were seronegative in the windows 60-119 days, 120-179 days and 180-240 days after PCR, respectively. In severe patients, these numbers were 1.9 %, 10.8 % and 29.4 % respectively (p < 0.05 each). Antibody levels were significantly higher in severe patients compared to mild patients in each 60 day window (p < 0.001 each).

Conclusions: SARS-CoV-2 anti-N IgG antibody levels steadily decreased after 2 months up to 8 months post PCR. Of severe COVID-19 patients, 70.6 % remained positive up to eight months after infection. Antibody levels were significantly lower in mild SARS-CoV-2 infected patients and 61.1 % became seronegative within 6 months after the first positive PCR.
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http://dx.doi.org/10.1016/j.jcv.2021.104765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891078PMC
March 2021

Aspiration Pneumonia After External Dacryocystorhinostomy Under Local Anesthesia Without Sedation: A Case Report.

Ophthalmic Plast Reconstr Surg 2021 May-Jun 01;37(3S):S162-S164

Department of Ophthalmology.

Amid the global coronavirus disease 2019 (COVID-19) outbreak, an 89-year-old male with chronic kidney disease presented with acute dacryocystitis and a persistent dry cough. After a course of antibiotics, external dacryocystorhinostomy was performed under local anesthesia without sedation. During planned hemodialysis in the early hours after the procedure, the patient developed nausea and hematemesis followed by severe dyspnea and hypoxemia. The patient was diagnosed with aspiration pneumonia, a previously unreported complication in lacrimal surgery.
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http://dx.doi.org/10.1097/IOP.0000000000001836DOI Listing
May 2021

The impact of the COVID-19 pandemic on the emotional well-being and home treatment of Belgian patients with cystic fibrosis, including transplanted patients and paediatric patients.

J Cyst Fibros 2020 11 31;19(6):880-887. Epub 2020 Jul 31.

Pulmonologist, University Hospitals Leuven, Leuven, Belgium.

Background: Little is known about the impact of COVID-19 on patients with cystic fibrosis (CF), despite being considered a high-risk group. This study explored the early impact of COVID-19 on the emotional well-being of patients and self-reported changes in their home therapy since the start of the pandemic.

Methods: Adult patients with CF, lung-transplanted (LTX) CF patients and parents of children with CF completed an online questionnaire, securely linked to their medical files. The questionnaire covered the emotional impact of the pandemic, changes in CF and LTX treatment, changes in health-protecting behaviours and CF-related concerns, and their perception of their COVID-19 status.

Results: The response rate was 63% (80 CF, 66 LTX and 73 parents). A wide range of illness severity was included. None of the respondents had contracted COVID-19 and all strictly followed the social distancing rules. There was evident psychological impact, with many reporting increased stress, fear and worry about CF and the future. Changes in treatment were positive, including more physiotherapy for adults and better-quality nebulizing. Changes in routine were reported, such as different treatment timing. Adult patients and parents had cancelled their CF appointments more often since the start of the pandemic.

Conclusions: The initial psychological impact of COVID-19 was evident. The impact on home treatment was reassuringly small. Psychological care is needed for patients suffering prolonged psychological impact, and CF teams need to contextualize the information that patients and parents receive from the media and support them to balance the perceived risk with true risk.
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http://dx.doi.org/10.1016/j.jcf.2020.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834420PMC
November 2020

COVID-19 in lung transplant patients: A case series.

Am J Transplant 2020 11 29;20(11):3234-3238. Epub 2020 Aug 29.

Department of Respiratory Diseases, University Hospital Gasthuisberg, Leuven, Belgium.

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome.
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http://dx.doi.org/10.1111/ajt.16212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404955PMC
November 2020

Clinical relevance of pulmonary non-tuberculous mycobacterial isolates in three reference centres in Belgium: a multicentre retrospective analysis.

BMC Infect Dis 2019 Dec 17;19(1):1061. Epub 2019 Dec 17.

Department of Respiratory Diseases, University Hospitals Leuven, Herestraat 49, B3000, Leuven, Belgium.

Background/objectives: Assessing the clinical relevance of non-tuberculous mycobacteria (NTM) isolated from respiratory samples can be challenging. The epidemiology and pathogenicity of NTM species vary geographically. We aimed to outline the clinical relevance and associated radiological patterns of NTM species isolated in Belgium.

Methods: We performed a retrospective multicentre analysis of all patients identified from the laboratory database with > 1 respiratory sample growing NTM from January 2010 through December 2017. We collected clinical, radiological and microbiological data through medical record review and assessed clinical relevance according to ATS/IDSA criteria for NTM pulmonary disease (NTM-PD).

Results: Of the 384 unique patients, 60% were male, 56% had a smoking history and 61% had pre-existing lung disease. Mycobacterium avium complex (MAC), M. gordonae and M. xenopi were the most frequently isolated species: 53, 15 and 8% respectively. 43% of patients met ATS/IDSA criteria, of whom 28% presented with fibrocavitary disease. Weight loss, fever, nodular bronchiectatic and fibrocavitary lesions on chest CT, and a positive acid-fast bacilli (AFB) stain were significantly associated with NTM-PD. The species with the highest pathogenic potential were M. abscessus (11/12), M. malmoense (6/7) and M. intracellulare (41/64).

Conclusion: In our study, MAC was the most commonly isolated NTM species, but M. abscessus and M. malmoense showed the highest probability of being clinically relevant. Clinical relevance varied not only by species but also by radiological findings on chest CT and AFB staining. Clinicians should consider these elements in their treatment decision making. Prospective data including clinical outcome are needed to provide more robust evidence.
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http://dx.doi.org/10.1186/s12879-019-4683-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918577PMC
December 2019

Defining Polysaccharide Antibody Deficiency: Measurement of Anti-Pneumococcal Antibodies and Anti-Salmonella typhi Antibodies in a Cohort of Patients with Recurrent Infections.

J Clin Immunol 2020 01 8;40(1):105-113. Epub 2019 Nov 8.

Inborn errors of immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Background: The correlation between different methods for the detection of pneumococcal polysaccharide vaccine (PPV) responses to diagnose specific polysaccharide antibody deficiency (SAD) is poor and the criteria for defining a normal response lack consensus. We previously proposed fifth percentile (p5) values of PPV responses as a new cutoff for SAD.

Objective: To analyze the association of SAD (determined by either World Health Organization (WHO)-standardized ELISA or multiplex bead-based assay) with abnormal response to Salmonella (S.) typhi Vi vaccination in a cohort of patients with recurrent infections.

Methods: Ninety-four patients with a clinical history suggestive of antibody deficiency received PPV and S. typhi Vi vaccines. Polysaccharide responses to either 3 or 18 pneumococcal serotypes were measured by either the WHO ELISA or a multiplex in-house bead-based assay. Anti-S. typhi Vi IgG were measured by a commercial ELISA kit. Allohemagglutinins (AHA) were measured by agglutination method.

Results: Based on the American Academy of Allergy, Asthma and Immunology (AAAAI) criteria for WHO ELISA, 18/94 patients were diagnosed with SAD and 22/93 based on serotype-specific p5 cutoffs for bead-based assay. The association between the two methods was significant, with 10 subjects showing abnormal response according to both techniques. Abnormal response to S. typhi Vi vaccination was found in 7 patients, 6 of which had SAD. No correlation was found between polysaccharide response and AHA, age, or clinical phenotype.

Conclusion: The lack of evidence-based gold standards for the diagnosis of SAD represents a challenge in clinical practice. In our cohort, we confirmed the insufficient correlation between different methods of specific PPV response measurement, and showed that the S. typhi Vi response was not contributive. Caution in the interpretation of results is warranted until more reliable diagnostic methods can be validated.
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http://dx.doi.org/10.1007/s10875-019-00691-8DOI Listing
January 2020

Performance of algorithms for tuberculosis active case finding in underserved high-prevalence settings in Cambodia: a cross-sectional study.

Glob Health Action 2019 ;12(1):1646024

Infectious Disease Department, Sihanouk Hospital Center of HOPE , Phnom Penh , Cambodia.

: Most studies evaluate active case findings (ACF) for bacteriologically confirmed TB. Adapted diagnostic approaches are needed to identify cases with lower bacillary loads. : To assess the likelihood of diagnosing all forms of TB, including clinically diagnosed pulmonary and extra-pulmonary TB, using different ACF algorithms in Cambodia. : Clients were stratified into 'high-risk' (presumptive TB plus TB contact, or history of TB, or presumptive HIV infection; n = 12,337) and 'moderate-risk' groups (presumptive TB; n = 28,804). Sputum samples were examined by sputum smear microscopy (SSM) or Xpert MTB/RIF (Xpert). Initially, chest X-ray using a mobile radiography unit was a follow-up test after a negative sputum examination [algorithms A (Xpert/X-ray) and B (SSM/X-ray)]. Subsequently, all clients received an X-ray [algorithms C (X-ray+Xpert) and D (Xray+SSM/Xpert)]. X-rays were interpreted on the spot. : Between 25 August 2014 and 31 March 2016, 2217 (5.4%) cases with all forms of TB cases were diagnosed among 41,141 adults. The majority of TB cases (1488; 67.1%) were diagnosed using X-ray. When X-rays were taken and interpreted the same day the sputum was collected, same-day diagnosis more than doubled. Overall, the number needed to test (NNT) to diagnose one case was 18.6 (95%CI:17.9-19.2). In the high-risk group the NNT was lower [algorithm D: NNT = 17.3(15.9-18.9)] compared with the 'moderate-risk group' [algorithm D: NNT = 20.8(19.6-22.2)]. In the high-risk group the NNT was lower when using Xpert as an initial test [algorithm A: NNT = 12.2(10.8-13.9) or algorithm C: NNT = 11.2(9.6-13.0)] compared with Xpert as a follow-up test [algorithm D: NNT = 17.3(15.9-18.9)]. : To diagnose all TB forms, X-ray should be part of the diagnostic algorithm. The combination of X-ray and Xpert testing for high-risk clients was the most effective ACF approach in this setting.
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http://dx.doi.org/10.1080/16549716.2019.1646024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735356PMC
January 2020

Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials.

ERJ Open Res 2019 Feb 1;5(1). Epub 2019 Feb 1.

Primary Ciliary Dyskinesia Centre, Dept of Paediatric Respiratory Medicine, Imperial College and Royal Brompton Hospital, London, UK.

Pulmonary exacerbations are a cause of significant morbidity in patients with primary ciliary dyskinesia (PCD) and are frequently used as an outcome measure in clinical research into chronic lung diseases. So far, there has been no consensus on the definition of pulmonary exacerbations in PCD. 30 multidisciplinary experts and patients developed a consensus definition for children and adults with PCD. Following a systematic review, the panel used a modified Delphi process with a combination of face-to-face meetings and e-surveys to develop a definition that can be used in research settings for children and adults with PCD. A pulmonary exacerbation was defined by the presence of three or more of the following seven items: 1) increased cough, 2) change in sputum volume and/or colour, 3) increased shortness of breath perceived by the patient or parent, 4) decision to start or change antibiotic treatment because of perceived pulmonary symptoms, 5) malaise, tiredness, fatigue or lethargy, 6) new or increased haemoptysis, and 7) temperature >38°C. The consensus panel proposed that the definition should be used for future clinical trials. The definition should be validated and the usability assessed during these studies.
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http://dx.doi.org/10.1183/23120541.00147-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355979PMC
February 2019

Successful lung transplantation for chronic Mycobacterium abscessus infection in advanced cystic fibrosis, a case series.

Transpl Infect Dis 2019 Apr 13;21(2):e13046. Epub 2019 Jan 13.

Department of Pneumology, University Hospitals Leuven, Leuven, Belgium.

Pulmonary Mycobacterium abscessus infection in cystic fibrosis (CF) patients is difficult to treat and considered a contra-indication for lung transplantation in most centers. We present four CF patients with chronic pulmonary M abscessus infection, in whom lung transplantation was performed. Through intensive treatment before transplantation, we achieved control of the infection in all but one patient. After a mean of 16 months of follow up, 3 patients are doing well, without evidence of local or disseminated recurrence. One patient died early post-transplant due to an unrelated cause. These findings support the possibility of lung transplantation with favorable outcome in CF patients with M abscessus infection.
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http://dx.doi.org/10.1111/tid.13046DOI Listing
April 2019

Sensitization to as a risk factor for bronchiectasis in COPD.

Int J Chron Obstruct Pulmon Dis 2017 31;12:2629-2638. Epub 2017 Aug 31.

Department of Respiratory Diseases, University Hospitals Leuven.

Background: Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients. We hypothesized that sensitization to () is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.

Methods: This observational study investigated sensitization to in an outpatient clinical cohort of 300 COPD patients and 50 (ex-) smoking controls. Total IgE, -specific IgE against the crude extract and against the recombinant antigens and IgG were measured using ImmunoCAP fluoroenzyme immunoassay. Vitamin D was measured by radioimmunoassay, and computed tomography images of the lungs were scored using the modified Reiff score.

Results: Sensitization to occurred in 18% of COPD patients compared to 4% of controls (=0.0110). In all, 31 COPD patients (10%) were sensitized to the crude extract and 24 patients (8%) had only IgE against recombinant antigens. IgG levels were significantly higher in the COPD group (=0.0473). Within COPD, -sensitized patients were more often male (=0.0293) and more often had bronchiectasis (=0.0297). and were more prevalent in historical sputum samples of -sensitized COPD patients compared to -non-sensitized COPD patients (=0.0436). Vitamin D levels were comparable (=0.2057). Multivariate analysis demonstrated that sensitization to recombinant f1 or f3 had a 2.8-fold increased risk for bronchiectasis (=0.0030).

Conclusion: These results highlight a potential role for sensitization to in COPD-related bronchiectasis.
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http://dx.doi.org/10.2147/COPD.S141695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587018PMC
June 2018

Using mobile phones to ensure that referred tuberculosis patients reach their treatment facilities: a call that makes a difference.

BMC Health Serv Res 2017 Aug 22;17(1):575. Epub 2017 Aug 22.

Médecins Sans Frontiéres, Brussels Operational Centre (Operational research), Luxembourg city, Luxembourg.

Background: Over the last decade, the availability and use of mobile phones have grown exponentially globally and in Cambodia. In the Sihanouk Hospital Centre of Hope(SHCH) in Cambodia about half of all tuberculosis patients referred out to peripheral health facilities for TB treatment initiation or continuation were lost to contact after referral ranging from 19 to 69% between 2008 and 2013. To address this, we implemented a mobile phone-based patient tracking intervention. Here, we report the number and proportion of referred TB patients who could be contacted through a mobile phone and retained in care after the introduction of mobile phone tracking.

Methods: A descriptive study involving follow-up of TB patients referred out from SHCH to peripheral health facilities during May-October 2014. Standard operating procedures were used to contact individual patients and/or health facilities using a mobile phone.

Results: Among 109 TB patients referred to peripheral health facilities, 107(98%) had access to a mobile phone of whom, 103(97%) could be contacted directly while 5(2%) were contacted through their health care providers. A total of 108(99%) of 109 referred TB patients in intervention period were thus placed on TB treatment.

Conclusions: This study provides preliminary, but promising evidence that using mobile phones was accompanied with improved retention of referred TB patients compared to historical cohorts. Given the limitations associated with historical controls, we need better designed studies with larger sample size to strengthen the evidence before national scale-up.
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http://dx.doi.org/10.1186/s12913-017-2511-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567436PMC
August 2017

Fifth Percentile Cutoff Values for Antipneumococcal Polysaccharide and Anti- Vi IgG Describe a Normal Polysaccharide Response.

Front Immunol 2017 12;8:546. Epub 2017 May 12.

Department Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium.

Background: Serotype-specific antibody responses to unconjugated pneumococcal polysaccharide vaccine (PPV) evaluated by a World Health Organization (WHO)-standardized enzyme-linked immunosorbent assay (ELISA) are the gold standard for diagnosis of specific polysaccharide antibody deficiency (SAD). The American Academy of Allergy, Asthma and Immunology (AAAAI) has proposed guidelines to interpret the PPV response measured by ELISA, but these are based on limited evidence. Additionally, ELISA is costly and labor-intensive. Measurement of antibody response to () Vi vaccine and serum allohemagglutinins (AHA) have been suggested as alternatives. However, there are no large cohort studies and cutoff values are lacking.

Objective: To establish cutoff values for antipneumococcal polysaccharide antibody response, anti- Vi antibody, and AHA.

Methods: One hundred healthy subjects (10-55 years) were vaccinated with PPV and Vi vaccine. Blood samples were obtained prior to and 3-4 weeks after vaccination. Polysaccharide responses to 3 serotypes were measured by WHO ELISA and to 12 serotypes by an in-house bead-based multiplex assay. Anti- Vi IgG were measured with a commercial ELISA kit. AHA were measured by agglutination method.

Results: Applying AAAAI criteria, 30% of healthy subjects had a SAD. Using serotype-specific fifth percentile (p5) cutoff values for postvaccination IgG and fold increase pre- over postvaccination, only 4% of subjects had SAD. One-sided 95% prediction intervals for anti- Vi postvaccination IgG (≥11.2 U/ml) and fold increase (≥2) were established. Eight percent had a response to Vi vaccine below these cutoffs. AHA titer p5 cutoffs were ½ for anti-B and ¼ for anti-A.

Conclusion: We establish reference cutoff values for interpretation of PPV response measured by bead-based assay, cutoff values for Vi vaccine responses, and normal values for AHA. For the first time, the intraindividual consistency of all three methods is studied in a large cohort.
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http://dx.doi.org/10.3389/fimmu.2017.00546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427071PMC
May 2017

Implementation of isoniazid preventive therapy in an HIV clinic in Cambodia: high rates of discontinuation when combined with antiretroviral therapy.

Trop Med Int Health 2015 Dec 19;20(12):1823-31. Epub 2015 Oct 19.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Objective: Data on feasibility and completion rates of isoniazid preventive therapy (IPT) in HIV-infected patient in Asia are limited. Within a hospital-based HIV programme in Phnom Penh, Cambodia, we determined the proportion completing IPT and reasons for non-completion.

Methods: Retrospective cohort study using HIV/IPT programme data, including all adults starting IPT (300 mg/day self-administered for 24 weeks) from February 2011 to March 2013. All patients underwent symptom screening and further investigations as indicated. After ruling out tuberculosis (TB), IPT was started, with monthly follow-up visits. As per national guideline, IPT was only prescribed for ART-naïve patients. IPT completion was defined as taking IPT for at least 22 of the planned 24 weeks. Stavudine/lamivudine/nevirapine was the preferential first-line ART regimen.

Results: Among 445 ART-naïve patients starting IPT (median age: 35 years (IQR: 31-43), median CD4 count 354 cells/μl (IQR 215-545) and 288 (65%) were female), 214 (48%) started ART after a median of 4 weeks (IQR 2-6) on IPT ('concurrent ART'). Overall, 348 (78%) completed IPT. Among individuals with concurrent ART, the completion rate was 73% (157/214). Those without concurrent ART had a higher completion rate (83%; 191/231; P 0.017). The main reason for non-completion with concurrent ART was drug toxicity (mainly hepatotoxicity/rash), occurring in 22% (48/214). Without concurrent ART, the main reason for non-completion was loss to follow-up (16/231; 7%). Fourteen (3%) patients were diagnosed with TB while on IPT, of whom three had a positive TB culture at baseline. An additional 14 TB cases were diagnosed after IPT completion; four were bacteriologically confirmed.

Conclusion: Although overall completion rates were acceptable, IPT discontinuation due to drug toxicity was common in patients subsequently initiating ART. Future studies should evaluate whether this relates to IPT, ARVs or both, and whether the increased toxicity would justify delaying IPT initiation until stabilisation on ART.
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http://dx.doi.org/10.1111/tmi.12609DOI Listing
December 2015

Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.

PLoS One 2015 29;10(7):e0130179. Epub 2015 Jul 29.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: While community-based active case finding (ACF) for tuberculosis (TB) holds promise for increasing early case detection among hard-to-reach populations, limited data exist on the acceptability of active screening. We aimed to identify barriers and explore facilitators on the pathway from diagnosis to care among TB patients and health providers.

Methods: Mixed-methods study. We administered a survey questionnaire to, and performed in-depth interviews with, TB patients identified through ACF from poor urban settlements in Phnom Penh, Cambodia. Additionally, we conducted focus group discussions and in-depth interviews with community and public health providers involved in ACF, respectively.

Results: Acceptance of home TB screening was strong among key stakeholders due to perceived reductions in access barriers and in direct and indirect patient costs. Privacy and stigma were not an issue. To build trust and facilitate communication, the participation of community representatives alongside health workers was preferred. Most health providers saw ACF as complementary to existing TB services; however, additional workload as a result of ACF was perceived as straining operating capacity at public sector sites. Proximity to a health facility and disease severity were the strongest determinants of prompt care-seeking. The main reasons reported for delays in treatment-seeking were non-acceptance of diagnosis, high indirect costs related to lost income/productivity and transportation expenses, and anticipated side-effects from TB drugs.

Conclusions: TB patients and health providers considered home-based ACF complementary to facility-based TB screening. Strong engagement with community representatives was believed critical in gaining access to high risk communities. The main barriers to prompt treatment uptake in ACF were refusal of diagnosis, high indirect costs, and anticipated treatment side-effects. A patient-centred approach and community involvement were essential in mitigating barriers to care in marginalised communities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130179PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519312PMC
April 2016

Community-based active tuberculosis case finding in poor urban settlements of Phnom Penh, Cambodia: a feasible and effective strategy.

PLoS One 2014 27;9(3):e92754. Epub 2014 Mar 27.

Clinical Sciences Department, Institute of Tropical Medicine, Antwerp, Belgium.

Background: In light of the limitations of the current case finding strategies and the global urgency to improve tuberculosis (TB) case-detection, a renewed interest in active case finding (ACF) has risen. The WHO calls for more evidence on innovative ways of TB screening, especially from low-income countries, to inform global guideline development. We aimed to assess the feasibility of community-based ACF for TB among the urban poor in Cambodia and determine its impact on case detection, treatment uptake and outcome.

Methods: Between 9/2/2012-31/3/2013 the Sihanouk Hospital Center of HOPE conducted a door-to-door survey for TB in deprived communities of Phnom Penh. TB workers and community health volunteers performed symptom screening, collected sputum and facilitated specimen transport to the laboratories. Fluorescence microscopy was introduced at three referral hospitals. The GeneXpert MTB/RIF assay (Xpert) was performed at tertiary level for individuals at increased risk of HIV-associated, drug-resistant or smear-negative TB. Mobile phone/short message system (SMS) was used for same-day issuing of positive results. TB workers contacted diagnosed patients and referred them for care at their local health centre.

Results: In 14 months, we screened 315.874 individuals; we identified 12.201 aged ≥ 15 years with symptoms suggestive of TB; 84% provided sputum. We diagnosed 783, including 737 bacteriologically confirmed, TB cases. Xpert testing yielded 41% and 48% additional diagnoses among presumptive HIV-associated and multidrug-resistant TB cases, respectively. The median time from sputum collection to notification (by SMS) of the first positive (microscopy or Xpert) result was 3 days (IQR 2-6). Over 94% commenced TB treatment and 81% successfully completed it.

Conclusion: Our findings suggest that among the urban poor ACF for TB, using a sensitive symptom screen followed by smear-microscopy and targeted Xpert, contributed to improved case detection of drug-susceptible and drug-resistant TB, shortening the diagnostic delay, and successfully bringing patients into care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092754PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968028PMC
December 2015

Timing of antiretroviral therapy in Cambodian hospital after diagnosis of tuberculosis: impact of revised WHO guidelines.

Bull World Health Organ 2013 Mar 12;91(3):195-206. Epub 2012 Dec 12.

Sihanouk Hospital Centre of Hope, St. 134, Sangkat Vealvong, Khan 7 Makara, Phnom Penh, Cambodia.

Objective: To determine if implementation of 2010 World Health Organization (WHO) guidelines on antiretroviral therapy (ART) initiation reduced delay from tuberculosis diagnosis to initiation of ART in a Cambodian urban hospital.

Methods: A retrospective cohort study was conducted in a nongovernmental hospital in Phnom Penh that followed new WHO guidelines in patients with human immunodeficiency virus (HIV) and tuberculosis. All ART-naïve, HIV-positive patients initiated on antituberculosis treatment over the 18 months before and after guideline implementation were included. A competing risk regression model was used.

Findings: After implementation of the 2010 WHO guidelines, 190 HIV-positive patients with tuberculosis were identified: 53% males; median age, 38 years; median baseline CD4+ T-lymphocyte (CD4+ cell) count, 43 cells/µL. Before implementation, 262 patients were identified; 56% males; median age, 36 years; median baseline CD4+ cell count, 59 cells/µL. With baseline CD4+ cell counts ≤ 50 cells/µL, median delay to ART declined from 5.8 weeks (interquartile range, IQR: 3.7-9.0) before to 3.0 weeks (IQR: 2.1-4.4) after implementation (P < 0.001); with baseline CD4+ cell counts > 50 cells/µL, delay dropped from 7.0 (IQR: 5.3-11.3) to 3.6 (IQR: 2.9-5.3) weeks (P < 0.001). The probability of ART initiation within 4 and 8 weeks after tuberculosis diagnosis rose from 23% and 65%, respectively, before implementation, to 62% and 90% after implementation. A non-significant increase in 6-month retention and antiretroviral substitution was seen after implementation.

Conclusion: Implementation of 2010 WHO recommendations in a routine clinical setting shortens delay to ART. Larger studies with longer follow-up are needed to assess impact on patient outcomes.
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http://dx.doi.org/10.2471/BLT.12.111153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590623PMC
March 2013

Incidence and risk factors for tuberculosis in HIV-infected patients while on antiretroviral treatment in Cambodia.

Trans R Soc Trop Med Hyg 2013 Apr 16;107(4):235-42. Epub 2013 Jan 16.

Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia.

Background: Given the lack of detailed studies on tuberculosis (TB) in patients on antiretroviral treatment (ART) in South-East Asia, we aimed to determine the incidence and risk factors for early (after ≤6 months of ART) and late (after >6 months of ART) incident TB in Cambodia.

Methods: We conducted a retrospective analysis of all patients started on ART at a non-governmental hospital in Phnom Penh (March 2003-December 2010). TB diagnosis was performed according to WHO algorithms. Risk factor analysis was performed using multivariate Cox regression modeling.

Results: Overall, 2984 patients started ART. The median baseline CD4 count was 89 cells µl(-1) (IQR 25-209), median age 34 years (IQR 29-40). Fifty-three percent of the patients were female. Median follow-up time on ART was 2.4 years. In addition to 932 (31.2%) patients already on TB treatment at ART initiation, 313 (10.5%) developed TB, with an overall incidence rate of 3.9/100 patient-years. Of those developing TB, 179 (6.0%) patients were diagnosed with early TB and 134 (4.5%) with late TB, corresponding with a rate of 13.5 and 2.0 per 100 patient-years respectively. Risk factors for early TB included low body mass index, low baseline CD4 count and low hemoglobin levels. Low on-treatment CD4 counts and hemoglobin levels, being underweight while on ART and prevalent TB were identified as risk factors for late TB.

Conclusion: The incidence of early TB was high, and predominantly associated with advanced HIV progression markers. Earlier ART initiation and enhanced TB screening prior to and after ART initiation is warranted. Late TB amounts to almost half of the total TB burden, meriting specific preventive and diagnostic approaches.
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http://dx.doi.org/10.1093/trstmh/trt001DOI Listing
April 2013

Incidence and risk factors of serious adverse events during antituberculous treatment in Rwanda: a prospective cohort study.

PLoS One 2011 18;6(5):e19566. Epub 2011 May 18.

Internal Medicine Department, Centre Hospitalier Universitaire de Kigali, Kigali, Rwanda.

Background: Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome.

Methods And Findings: Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28-40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm(3) (IQR 44-248 cells/mm(3)). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4-8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1-3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1-3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0-2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3-3.0).

Conclusion: Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097195PMC
September 2011

The immune reconstitution inflammatory syndrome and antiretroviral therapy.

Br J Hosp Med (Lond) 2010 Dec;71(12):691-7

Institute of Tropical Medicine, Department of Clinical Sciences, University of Antwerp, Faculty of Medicine, Antwerp, Belgium.

Although generally mild, severe immune reconstitution inflammatory syndrome may complicate antiretroviral therapy, and it may be difficult to differentiate from treatment failure or toxicity. This article looks at diagnostic and therapeutic challenges of severe infectious manifestations of immune reconstitution inflammatory syndrome.
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http://dx.doi.org/10.12968/hmed.2010.71.12.691DOI Listing
December 2010

The role of PET scan in diagnosis, staging, and management of non-small cell lung cancer.

Oncologist 2004 ;9(6):633-43

Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

Positron emission tomography (PET) is now an important cancer imaging tool, both for diagnosis and staging, as well as offering prognostic information based on response. This report attempts to comprehensively review the value of PET in the locoregional and distant staging of non-small cell lung cancer (NSCLC), illustrate the potential effects on patient management, and give a short overview of newer applications. PET sets the gold standard in the evaluation of an indeterminate solitary pulmonary nodule or mass, where PET has proven to be significantly more accurate than computed tomography (CT) in the distinction between benign and malignant lesions. In the evaluation of metastatic spread to locoregional lymph nodes, PET is significantly more accurate than CT, so that invasive surgical staging may be omitted in many patients with negative mediastinal PET images. In patients with positive mediastinal PET images, invasive surgical staging remains mandatory because of the possibility of false-positive findings due to inflammatory nodes or granulomatous disorders. In the search for metastatic spread, PET is a useful adjunct to conventional imaging. This may be due to the finding of unexpected metastatic lesions or due to exclusion of malignancy in lesions that are equivocal on standard imaging. However, at this time, PET does not replace conventional imaging. Large-scale randomized studies are currently examining whether PET staging will actually improve the appearance of lung cancer outcome.
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http://dx.doi.org/10.1634/theoncologist.9-6-633DOI Listing
March 2005
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