Publications by authors named "Lyly Annina"

10 Publications

  • Page 1 of 1

Lung function and side effects of Aspirin desensitization: a real world study.

Eur Clin Respir J 2021 Jan 11;8(1):1869408. Epub 2021 Jan 11.

Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

: NSAID-exacerbated respiratory disease (N-ERD) is mainly treated with topical and oral corticosteroids, as well as acetylsalicylic acid (ASA) treatment after desensitization (ATAD). During desensitization and ATAD, it is common to experience an exacerbation of respiratory symptoms and other side effects, which may lead to cessation of treatment. : The aim of this retrospective follow-up study was to evaluate the effect of ATAD on lung functions and respiratory symptoms, and to clarify the occurrence of adverse events. s: We analysed the patient data of 67 patients treated with ASA desensitization between 2006 and 2016 in three hospitals, concerning adverse events, respiratory symptoms, lung function tests, and reasons for discontinuation. : 26 patients discontinued AD or ATAD. The most common reasons for discontinuation were lack of response (9%) and side effects (18%). ATAD did not affect lung function values in the follow-up of up to 5 years. Upper respiratory symptoms improved in 31 (52%) and lower respiratory symptoms (LRS) in 7 (10%) cases. Side effects occurred in 42 (63%) cases, the most common being dyspepsia and lower respiratory symptoms. : Our study suggests that ATAD has little effect on lower airway functions. Side effects were common, and discontinuation rates high.
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http://dx.doi.org/10.1080/20018525.2020.1869408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808387PMC
January 2021

Factors affecting upper airway control of NSAID-exacerbated respiratory disease: A real-world study of 167 patients.

Immun Inflamm Dis 2021 Mar 5;9(1):80-89. Epub 2021 Jan 5.

Inflammation Center, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N-ERD forms a major public health problem due to frequent and difficult-to-treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N-ERD.

Methods: Retrospective patient record data (patient characteristics, prior sinus surgeries, follow-up data in 2020) from 167 N-ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N-ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016-2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models.

Results: Nasal polyp eosinophilia increased the risk of revision surgery during the follow-up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23-8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04-2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07-4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23-6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98-4.70) were associated with the use of OCS/biological therapy during the follow-up, but not with high number of antibiotics.

Conclusions: Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N-ERD. These factors might be clinically useful in risk-estimation of uncontrolled disease and for organizing follow-ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N-ERD.
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http://dx.doi.org/10.1002/iid3.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860608PMC
March 2021

Monoclonal Antibodies and Airway Diseases.

Int J Mol Sci 2020 Dec 13;21(24). Epub 2020 Dec 13.

Inflammation Centre, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, P.O. Box 160, 00029 HUS Helsinki, Finland.

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome-environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.
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http://dx.doi.org/10.3390/ijms21249477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763928PMC
December 2020

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 Oct 28;10(1):45. Epub 2020 Oct 28.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
October 2020

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 28;10:45. Epub 2020 Oct 28.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592594PMC
October 2020

Childhood nontuberculous mycobacterial lymphadenitis-observation alone is a good alternative to surgery.

Int J Pediatr Otorhinolaryngol 2020 Feb 12;129:109778. Epub 2019 Nov 12.

Department of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address:

Objective: Cervicofacial lymphadenitis caused by nontuberculous mycobacteria (NTM) is commonly treated with surgery or antimicrobial therapy. The aim of this study was to analyze the utility of our new blood-based diagnostic method and the treatment protocol, surgery or observation alone, in NTM lymphadenitis in children.

Methods: All patients under 16 years of age with cervicofacial NTM lymphadenitis diagnosed and treated at Children's Hospital or at the Department of Otorhinolaryngology, Helsinki University Hospital (Helsinki, Finland) in 2007-2017 were retrospectively reviewed.

Results: Fifty-two patients, 33 (63%) of whom were girls, were included in the study. The median age at initial presentation of the NTM lymphadenitis was 2.9 years. The novel blood-test had been performed on 49 (94%) of the patients and in all of them it was indicative of NTM infection. A sample for mycobacterial culture was available from 34 patients, and Mycobacterium avium was the most common species detected. Most patients (n = 33, 63%) were treated conservatively with observation alone. Of these, nine patients (27%) did not develop a skin fistula, and the lymphadenitis resolved without drainage.

Conclusions: The novel blood test is clinically feasible method for diagnosing childhood cervicofacial NTM lymphadenitis noninvasively. Observation alone is a good alternative to surgery, without the risk of complications.
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http://dx.doi.org/10.1016/j.ijporl.2019.109778DOI Listing
February 2020

Plunging ranula - patient characteristics, treatment, and comparison between different populations.

Acta Otolaryngol 2017 Dec 28;137(12):1271-1274. Epub 2017 Jul 28.

a Department of Otorhinolaryngology - Head and Neck Surgery , Helsinki University Hospital and University of Helsinki , Helsinki , Finland.

Objectives: To review our clinical experience and characteristics of Finnish patients with plunging ranula and compare our results with reports from other populations.

Design: A retrospective study from the electronic hospital records between 2005 and 2016.

Setting: The Department of Otorhinolaryngology and Head and Neck Surgery of Helsinki University Hospital, Finland.

Results: We describe the characteristics and treatment of 41 patients with MRI-confirmed plunging ranula. Most of our patients were young adults and 88% of them were male. Surgery and sclerotherapy were used for treatment.

Conclusions: The vast majority of Finnish plunging ranula patients in our cohort were male, suggesting significant population-related differences in plunging ranula gender distribution. Transoral surgery seemed to result in lowest recurrence rate and was the most common treatment in our clinic.
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http://dx.doi.org/10.1080/00016489.2017.1357082DOI Listing
December 2017

Novel interactions of CLN5 support molecular networking between Neuronal Ceroid Lipofuscinosis proteins.

BMC Cell Biol 2009 Nov 26;10:83. Epub 2009 Nov 26.

National Institute for Health and Welfare (THL), Biomedicum Helsinki, Finland and FIMM, Institute for Molecular Medicine in Finland.

Background: Neuronal ceroid lipofuscinoses (NCLs) comprise at least eight genetically characterized neurodegenerative disorders of childhood. Despite of genetic heterogeneity, the high similarity of clinical symptoms and pathology of different NCL disorders suggest cooperation between different NCL proteins and common mechanisms of pathogenesis. Here, we have studied molecular interactions between NCL proteins, concentrating specifically on the interactions of CLN5, the protein underlying the Finnish variant late infantile form of NCL (vLINCLFin).

Results: We found that CLN5 interacts with several other NCL proteins namely, CLN1/PPT1, CLN2/TPP1, CLN3, CLN6 and CLN8. Furthermore, analysis of the intracellular targeting of CLN5 together with the interacting NCL proteins revealed that over-expression of PPT1 can facilitate the lysosomal transport of mutated CLN5FinMajor, normally residing in the ER and in the Golgi complex. The significance of the novel interaction between CLN5 and PPT1 was further supported by the finding that CLN5 was also able to bind the F1-ATPase, earlier shown to interact with PPT1.

Conclusion: We have described novel interactions between CLN5 and several NCL proteins, suggesting a modifying role for these proteins in the pathogenesis of individual NCL disorders. Among these novel interactions, binding of CLN5 to CLN1/PPT1 is suggested to be the most significant one, since over-expression of PPT1 was shown to influence on the intracellular trafficking of mutated CLN5, and they were shown to share a binding partner outside the NCL protein spectrum.
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http://dx.doi.org/10.1186/1471-2121-10-83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790443PMC
November 2009

Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism.

Hum Mol Genet 2008 May 1;17(10):1406-17. Epub 2008 Feb 1.

National Public Health Institute and FIMM, Institute for Molecular Medicine, Biomedicum Helsinki, PO Box 104, FIN-00251 Helsinki, Finland.

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disease caused by deficiency of palmitoyl protein thioesterase 1 (PPT1). INCL results in dramatic loss of thalamocortical neurons, but the disease mechanism has remained elusive. In the present work we describe the first interaction partner of PPT1, the F(1)-complex of the mitochondrial ATP synthase, by co-purification and in vitro-binding assays. In addition to mitochondria, subunits of F(1)-complex have been reported to localize in the plasma membrane, and to be capable of acting as receptors for various ligands such as apolipoprotein A-1. We verified here the plasma membrane localization of F(1)-subunits on mouse primary neurons and fibroblasts by cell surface biotinylation and TIRF-microscopy. To gain further insight into the Ppt1-mediated properties of the F(1)-complex, we utilized the Ppt1-deficient Ppt1(Delta ex4) mice. While no changes in the mitochondrial function could be detected in the brain of the Ppt1(Delta ex4) mice, the levels of F(1)-subunits alpha and beta on the plasma membrane were specifically increased in the Ppt1(Delta ex4) neurons. Significant changes were also detected in the apolipoprotein A-I uptake by the Ppt1(Delta ex4) neurons and the serum lipid composition in the Ppt1(Delta ex4) mice. These data indicate neuron-specific changes for F(1)-complex in the Ppt1-deficient cells and give clues for a possible link between lipid metabolism and neurodegeneration in INCL.
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http://dx.doi.org/10.1093/hmg/ddn028DOI Listing
May 2008

Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1)--distinct characteristics in neurons.

BMC Cell Biol 2007 Jun 12;8:22. Epub 2007 Jun 12.

Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki, Finland.

Background: Neuronal ceroid lipofuscinoses (NCLs) are collectively the most common type of recessively inherited childhood encephalopathies. The most severe form of NCL, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). The deficiency of PPT1 causes a specific death of neocortical neurons by a mechanism, which is currently unclear. To understand the function of PPT1 in more detail, we have further analyzed the basic properties of the protein, especially focusing on possible differences in non-neuronal and neuronal cells.

Results: Our study shows that the N-glycosylation of N197 and N232, but not N212, is essential for PPT1's activity and intracellular transport. Deglycosylation of overexpressed PPT1 produced in neurons and fibroblasts demonstrates differentially modified PPT1 in different cell types. Furthermore, antibody internalization assays showed differences in PPT1 transport when compared with a thoroughly characterized lysosomal enzyme aspartylglucosaminidase (AGA), an important observation potentially influencing therapeutic strategies. PPT1 was also demonstrated to form oligomers by size-exclusion chromatography and co-immunoprecipitation assays. Finally, the consequences of disease mutations were analyzed in the perspective of our new results, suggesting that the mutations increase both the degree of glycosylation of PPT1 and its ability to form complexes.

Conclusion: Our current study describes novel properties for PPT1. We observe differences in PPT1 processing and trafficking in neuronal and non-neuronal cells, and describe for the first time the ability of PPT1 to form complexes. Understanding the basic characteristics of PPT1 is fundamental in order to clarify the molecular pathogenesis behind neurodegeneration in INCL.
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http://dx.doi.org/10.1186/1471-2121-8-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906764PMC
June 2007