Chronic Laryngitis
Chronic laryngitis is a persistent inflammation of the larynx, commonly known as the voice box, lasting for more than three weeks. This condition primarily affects the vocal cords, leading to voice changes and discomfort. Unlike acute laryngitis, which often resolves quickly, chronic laryngitis involves long-term irritation and structural changes to the laryngeal tissues.
The biological basis of chronic laryngitis involves sustained inflammation of the laryngeal mucosa. This inflammation can be triggered by various factors, including prolonged exposure to irritants such as cigarette smoke or environmental pollutants, chronic vocal abuse or overuse, gastroesophageal reflux disease (GERD), and recurrent infections. Over time, this chronic irritation can lead to changes in the vocal cord tissue, such as thickening, swelling, or the development of lesions, which impair their normal vibratory function.
Clinically, chronic laryngitis manifests with symptoms such as hoarseness (dysphonia), a persistent sore throat, frequent throat clearing, a dry cough, and a feeling of a lump in the throat. The severity of these symptoms can fluctuate, significantly impacting an individual’s ability to communicate effectively. Diagnosis typically involves a medical history, physical examination, and often a laryngoscopy to visualize the vocal cords and assess the extent of inflammation or tissue changes. Untreated chronic laryngitis can lead to more serious vocal cord pathologies, including polyps, nodules, or granulomas, and in rare cases, may obscure or contribute to the development of more serious conditions.
From a social perspective, chronic laryngitis can have a considerable impact on an individual’s quality of life. Voice is a fundamental tool for communication, and persistent hoarseness or discomfort can affect personal relationships, professional performance, and daily interactions. Professions that rely heavily on voice, such as teaching, singing, public speaking, or customer service, can be particularly affected, potentially leading to career limitations or changes. The social burden extends to the need for ongoing medical management and lifestyle adjustments to mitigate symptoms and prevent recurrence.
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of complex traits like chronic laryngitis presents several inherent challenges, primarily due to the intricate nature of these conditions, the methodologies employed in genetic research, and the diverse factors that influence their manifestation.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Genome-wide association studies (GWAS) are designed to identify common genetic variants associated with a trait, but they often require exceptionally large sample sizes to detect the typically small effect sizes of individual variants, especially for complex conditions such as chronic laryngitis[1]. Studies with insufficient statistical power may fail to identify true associations or, conversely, report inflated effect sizes for variants that achieve nominal significance, which can be misleading without proper replication. Furthermore, initial findings from discovery cohorts necessitate rigorous validation through independent replication studies to confirm their authenticity and generalizability, a process that is critical for distinguishing robust associations from false positives [2]. The absence of adequate replication across diverse populations or with different methodologies can limit the confidence in reported genetic associations and their clinical utility.
Phenotypic Heterogeneity and Generalizability
Section titled “Phenotypic Heterogeneity and Generalizability”A significant limitation in genetic research for chronic laryngitis lies in the precise definition and consistent measurement of the phenotype. Chronic laryngitis can encompass a spectrum of symptoms and underlying pathologies, making it challenging to establish uniform diagnostic criteria or severity scales across different research cohorts. This phenotypic heterogeneity can obscure true genetic signals, as distinct genetic factors might contribute to different subtypes or manifestations of the condition[3]. Additionally, genetic findings derived from studies predominantly involving populations of a specific ancestry may not be fully generalizable to other ethnic groups [4]. Differences in allele frequencies, linkage disequilibrium patterns, and environmental exposures across diverse populations can lead to variations in genetic architecture, potentially limiting the broader applicability and predictive power of identified genetic markers.
Incomplete Genetic Architecture and Environmental Interactions
Section titled “Incomplete Genetic Architecture and Environmental Interactions”Despite advances in identifying genetic loci, GWAS typically explains only a fraction of the heritability for complex traits, a phenomenon often referred to as “missing heritability.” This gap may be attributed to several factors, including the contribution of rare genetic variants, structural variations, complex gene-gene interactions, or epigenetic modifications that are not adequately captured by standard GWAS arrays [5]. Moreover, chronic laryngitis is profoundly influenced by a multitude of environmental factors such as vocal misuse, gastroesophageal reflux, smoking, and environmental irritants[6]. Disentangling the independent genetic effects from the confounding or interacting influences of these environmental exposures presents a substantial challenge. Comprehensive assessment of gene-environment interactions is crucial for a complete understanding of the disease etiology, as genetic predispositions may only manifest under specific environmental conditions, and vice versa.
Variants
Section titled “Variants”Genetic variations play a crucial role in an individual’s susceptibility to chronic inflammatory conditions, including chronic laryngitis. While the exact mechanisms are complex, single nucleotide polymorphisms (SNPs) within or near genes involved in inflammation, tissue maintenance, and cellular signaling can influence the risk and progression of such disorders. Studies have highlighted the genetic underpinnings of various respiratory conditions, providing a framework for understanding potential predispositions to chronic airway inflammation[3].
For instance, the NDST4 gene (N-deacetylase/N-sulfotransferase 4) is essential for the biosynthesis of heparan sulfate, a molecule critical for cell surface interactions and extracellular matrix structure, which modulates inflammatory responses. A variant like rs187967316 in NDST4 could potentially alter the structure or abundance of heparan sulfate, thereby influencing the severity or persistence of inflammation in the larynx. Similarly, the SS18 gene (SS18 Scaffold Protein) contributes to the SWI/SNF chromatin remodeling complex, which regulates gene expression by modifying chromatin structure. A variant such as rs184756987 in SS18 might lead to dysregulated gene expression patterns, affecting cell proliferation, differentiation, or inflammatory pathways within the laryngeal tissues. The genetic landscape of related conditions like chronic mucus hypersecretion emphasizes the broad impact of genetic variations on airway health [3].
Other variants influence gene regulation and cellular rhythm. The RORB gene (Retinoid-related orphan receptor beta) encodes a nuclear receptor involved in circadian rhythm regulation and neuronal development; its expression and function can impact inflammatory processes. A variant like rs565266096 in RORB could disrupt these regulatory roles, potentially affecting the larynx’s response to chronic irritation. Long non-coding RNAs (lncRNAs) such as those associated with LINC02466 (rs572966339 ) and LINC00303 (part of the rs144067010 locus with CBX1P3) are increasingly recognized for their roles in modulating gene expression, immune responses, and tissue homeostasis. Variations in these lncRNAs could alter their regulatory capacity, influencing inflammation or tissue repair in the vocal folds. Such genetic factors are widely recognized to affect airway responsiveness and chronic obstructive pulmonary disease (COPD), conditions that share inflammatory pathways with laryngitis[7].
The LSS gene (Lanosterol Synthase), found near SPATC1L and associated with rs796920051 , is a key enzyme in cholesterol biosynthesis, producing lanosterol, a precursor for steroids and other lipids. Variations in LSS could affect lipid metabolism, cell membrane integrity, or the production of steroid hormones, which are important modulators of inflammation. Dysregulation of these processes could contribute to the chronic inflammatory state seen in laryngitis. The collective impact of these diverse genetic factors highlights the complex interplay between an individual’s genetic makeup and their susceptibility to chronic inflammatory conditions affecting the respiratory system [1].
The provided research context does not contain specific information regarding the classification, definition, and terminology of ‘chronic laryngitis’. Therefore, this section cannot be completed based on the given materials.
Key Variants
Section titled “Key Variants”Causes
Section titled “Causes”Chronic laryngitis, characterized by persistent inflammation of the voice box, arises from a complex interplay of genetic predispositions, environmental exposures, and systemic health factors. Understanding these multifaceted causes is crucial for effective prevention and management.
Genetic Predisposition to Airway Inflammation
Section titled “Genetic Predisposition to Airway Inflammation”An individual’s genetic makeup plays a significant role in determining susceptibility to chronic laryngitis, often through influencing general airway health and immune responses. Genome-wide association studies (GWAS) have identified various genetic variants that contribute to the risk of chronic airway conditions, including chronic mucus hypersecretion, asthma, and chronic obstructive pulmonary disease (COPD), which are often linked to laryngeal irritation and inflammation[3]. For instance, the SATB1gene has been implicated in airway disease, suggesting a role in immune regulation or tissue development that could impact laryngeal resilience[3]. The polygenic nature of these conditions means that multiple inherited variants, each with a small effect, combine to confer an overall risk, affecting the body’s ability to clear irritants or mount an appropriate inflammatory response.
Furthermore, research indicates common genetic underpinnings for different airway diseases, such as asthma and COPD, implying shared pathways of susceptibility that could extend to chronic laryngitis[8]. These genetic factors may influence the integrity of the laryngeal mucosa, the production of protective mucus, or the sensitivity of the airways to external stimuli. Gene-gene interactions can further modulate this risk, where the combined effect of specific genetic variants is greater than their individual contributions, potentially leading to a more pronounced or persistent inflammatory state in the larynx.
Environmental Exposures and Lifestyle Factors
Section titled “Environmental Exposures and Lifestyle Factors”Environmental factors are primary drivers of chronic laryngitis, with chronic exposure to irritants being a key mechanism. Lifestyle choices, particularly smoking, are strongly associated with chronic airway inflammation, including conditions like chronic mucus hypersecretion and COPD, which can directly affect the larynx[9]. Inhaled irritants from tobacco smoke directly damage the delicate laryngeal lining, triggering a chronic inflammatory response and altered mucus production that manifests as persistent irritation and voice changes.
Beyond smoking, other environmental exposures such as air pollution, occupational irritants, and even dietary factors can contribute to chronic laryngeal inflammation. These external agents can induce oxidative stress, impair mucociliary clearance, and provoke an immune response in the larynx, leading to long-term tissue damage and dysfunction. The duration and intensity of these exposures often correlate with the severity and persistence of chronic laryngitis.
Gene-Environment Interactions
Section titled “Gene-Environment Interactions”The development of chronic laryngitis is frequently a result of intricate gene-environment interactions, where genetic predispositions modify an individual’s response to environmental triggers. For example, while smoking is a major risk factor, not all smokers develop severe chronic airway diseases, suggesting that genetic factors play a protective or exacerbating role[9]. Specific genetic variants can influence how effectively an individual metabolizes toxins, repairs cellular damage, or regulates inflammatory pathways in response to smoke or other irritants.
Studies on smoking behaviors and COPD have identified genetic loci, such as those near the nicotinic acetylcholine receptor, that are associated with smoking habits and susceptibility to airway damage [6]. This indicates that genetic factors can not only influence the physiological response to environmental exposures but also an individual’s propensity for engaging in certain damaging behaviors. The combination of genetic susceptibility and chronic environmental exposure, therefore, creates a heightened risk for persistent laryngeal inflammation.
Comorbid Conditions and Age-Related Influences
Section titled “Comorbid Conditions and Age-Related Influences”The presence of other health conditions, or comorbidities, significantly contributes to the risk and persistence of chronic laryngitis. Conditions such as asthma, chronic obstructive pulmonary disease (COPD), and chronic mucus hypersecretion are frequently observed alongside chronic laryngitis, as they share inflammatory pathways and can lead to irritation of the upper airways[8]. Systemic inflammation or reflux from gastrointestinal issues can also irritate the larynx, contributing to its chronic inflammation.
Age-related physiological changes also play a role in the etiology of chronic laryngitis. As individuals age, the tissues of the larynx may become less resilient, more susceptible to damage, and slower to repair, making them more vulnerable to chronic inflammation from various insults[10]. The cumulative effect of lifelong environmental exposures and the gradual decline in tissue repair mechanisms can lead to the development or exacerbation of chronic laryngitis in older individuals.
Cellular and Molecular Mechanisms of Airway Inflammation
Section titled “Cellular and Molecular Mechanisms of Airway Inflammation”Chronic laryngitis, like other chronic airway diseases, involves persistent inflammation at the cellular and molecular levels, disrupting normal laryngeal function. This inflammatory process often includes the activation of various immune cells and the release of pro-inflammatory mediators that perpetuate tissue damage and remodeling. Cellular functions such as epithelial barrier integrity and mucociliary clearance can be compromised, leading to a vicious cycle of irritation and inflammation. The sustained presence of inflammatory signals can alter regulatory networks within the laryngeal tissues, influencing cell proliferation, differentiation, and apoptosis, which are crucial for maintaining tissue homeostasis.
Genetic Susceptibility and Gene Regulation in Airway Disease
Section titled “Genetic Susceptibility and Gene Regulation in Airway Disease”Genetic factors play a significant role in an individual’s susceptibility to chronic airway conditions, including those that manifest as chronic laryngitis. Specific gene functions and their regulatory elements can influence the body’s response to environmental irritants and its predisposition to chronic inflammation. For instance, the gene SATB1 has been identified to have a genetic influence on airway disease, suggesting its role in modulating the immune response or tissue structure within the respiratory tract[3]. Furthermore, research indicates common genetic underpinnings between various chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), implying shared molecular pathways that could also contribute to chronic laryngitis[8]. Genetic variations can lead to altered gene expression patterns, affecting the production of proteins essential for airway defense, repair, and inflammation resolution.
Pathophysiology of Chronic Mucus Hypersecretion and Tissue Changes
Section titled “Pathophysiology of Chronic Mucus Hypersecretion and Tissue Changes”A hallmark of many chronic airway conditions, including aspects relevant to chronic laryngitis, is the pathophysiological process of chronic mucus hypersecretion (CMH). This condition is defined by the overproduction of mucus, evidenced by sputum production for a significant duration[3]. This hypersecretion represents a disruption in the homeostatic balance of airway defense mechanisms, where mucus, normally protective, becomes excessive and contributes to symptoms like chronic cough and throat clearing. At the tissue level, prolonged inflammation and mucus hypersecretion can lead to structural changes, such as goblet cell hyperplasia and submucosal gland enlargement, further exacerbating mucus production and impairing clearance. These ongoing disruptions can also contribute to altered airway responsiveness, where the airways become overly sensitive to various stimuli[7].
Key Biomolecules and Structural Components in Airway Health
Section titled “Key Biomolecules and Structural Components in Airway Health”The complex biology of chronic airway inflammation and mucus production involves numerous key biomolecules and structural components that regulate cellular processes and tissue integrity. Critical proteins, enzymes, and receptors mediate the inflammatory cascade and the production of mucus. For example, specific genes like IREB2 and GALC have been associated with aspects of chronic obstructive pulmonary disease, indicating their potential roles in structural or functional changes within the airways[11]. Additionally, structural components such as sarcoglycan delta (SGCD), which shows intense staining in airway smooth muscle bundles, highlight the importance of muscular and structural integrity in maintaining airway function and responsiveness[7]. These biomolecules and their interactions within signaling pathways are crucial targets for understanding the progression and potential treatment of chronic inflammatory conditions affecting the larynx.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”The development and persistence of chronic laryngitis involve a complex interplay of genetic predispositions, dysregulated signaling pathways, and altered molecular regulatory mechanisms within the laryngeal mucosa. Research into related chronic airway diseases provides insights into the potential pathways contributing to this condition.
Genetic Predisposition and Transcriptional Regulation in Airway Health
Section titled “Genetic Predisposition and Transcriptional Regulation in Airway Health”Genetic factors play a role in an individual’s susceptibility to chronic airway conditions, including those that may manifest as chronic laryngitis. For instance, the gene SATB1 (Special AT-rich sequence-binding protein 1) has been identified as having a “Genetic Influence… on Airway Disease”[3]. As a transcription factor, SATB1 likely plays a crucial role in regulating the expression of numerous genes involved in cellular development, immune response, and tissue maintenance within the airways. Dysregulation of such key transcriptional regulators can alter the fundamental gene expression programs in laryngeal cells, potentially leading to chronic inflammation, altered epithelial barrier function, or aberrant mucin production characteristic of chronic laryngitis. Understanding these genetic influences and their impact on transcription factor activity provides insight into the foundational regulatory mechanisms of airway health.
Signaling Cascades and Mucus Hypersecretion Pathways
Section titled “Signaling Cascades and Mucus Hypersecretion Pathways”Chronic laryngitis often involves persistent inflammation and, in some cases, excessive mucus production, a phenotype extensively studied in other chronic airway diseases. Genetic studies have investigated the underpinnings of “chronic mucus hypersecretion”[3]. While specific laryngeal signaling cascades are not detailed, the chronic nature of the condition implies sustained activation of intracellular signaling pathways that drive mucin gene expression and secretion from goblet cells and submucosal glands. These cascades, potentially initiated by chronic irritation or inflammatory mediators, can lead to a feedback loop where increased mucus contributes to irritation, perpetuating the inflammatory cycle. Identifying the specific receptors and downstream signaling molecules involved in these pathways is critical for understanding the persistent symptoms associated with chronic laryngitis.
Molecular Regulatory Mechanisms and Metabolic Insights in Chronic Airway Disease
Section titled “Molecular Regulatory Mechanisms and Metabolic Insights in Chronic Airway Disease”Beyond gene transcription, chronic airway diseases involve intricate molecular regulatory mechanisms, including protein modification and metabolic pathway regulation. Genes like IREB2 and GALC have been associated with pulmonary artery enlargement in chronic obstructive pulmonary disease, suggesting their broader involvement in chronic airway pathology[12]. IREB2 (Iron Responsive Element Binding Protein 2) is a key regulator of iron metabolism, indicating that metabolic shifts, such as altered iron homeostasis or energy metabolism, could contribute to cellular stress and inflammation in the larynx. GALC (Galactosylceramidase), a lysosomal enzyme, highlights the potential role of lipid metabolism and waste product clearance, where its dysregulation could lead to the accumulation of harmful substrates and impaired cellular function, thus fueling chronic inflammatory processes. These examples illustrate how diverse regulatory and metabolic pathways contribute to the complex molecular landscape of persistent airway conditions.
Systems-Level Integration and Disease Emergence
Section titled “Systems-Level Integration and Disease Emergence”Chronic laryngitis, like many complex diseases, emerges from the systems-level integration of multiple interacting pathways rather than a single molecular defect. The identification of “Common genes underlying asthma and COPD” suggests shared genetic susceptibilities and interconnected pathological networks across different chronic airway diseases[8]. This pathway crosstalk implies that dysregulation in one biological process, such as inflammation or epithelial repair, can impact others, leading to a cascade of events that collectively manifest as the chronic disease phenotype. The polygenic nature of chronic airway conditions, with “multiple risk loci for chronic obstructive pulmonary disease” identified, underscores how a combination of genetic variations and environmental exposures can converge to disrupt network interactions and overwhelm compensatory mechanisms, leading to the sustained inflammatory state characteristic of chronic laryngitis[13].
Frequently Asked Questions About Chronic Laryngitis
Section titled “Frequently Asked Questions About Chronic Laryngitis”These questions address the most important and specific aspects of chronic laryngitis based on current genetic research.
1. My mom has chronic laryngitis; will I definitely get it?
Section titled “1. My mom has chronic laryngitis; will I definitely get it?”Not necessarily, but you might have a higher predisposition. While chronic laryngitis is influenced by many environmental factors like smoking or vocal strain, genetic variations can increase your susceptibility. For example, differences in genes involved in inflammation or tissue maintenance, like NDST4, could make you more prone to developing the condition if exposed to triggers. So, while genetics play a role, it’s not a guarantee, and lifestyle choices are very important.
2. I don’t smoke, but why do I still have chronic laryngitis?
Section titled “2. I don’t smoke, but why do I still have chronic laryngitis?”Even without smoking, other factors can trigger chronic laryngitis, and your genetics might increase your susceptibility. Genes involved in how your body handles inflammation or maintains tissue, such as NDST4, can make you more sensitive to irritants like pollution, vocal overuse, or even acid reflux. So, even with a “clean” lifestyle, your genetic makeup could make you more vulnerable to developing the condition.
3. My friend sings more than me, but why do I get hoarse easily?
Section titled “3. My friend sings more than me, but why do I get hoarse easily?”Your individual genetic makeup can influence how your vocal cords respond to stress and inflammation. While your friend might have genes that help their laryngeal tissues recover more efficiently from vocal strain, your genes, perhaps involving specific variations in inflammation pathways or tissue maintenance like NDST4, could make your vocal cords more prone to irritation and swelling, leading to quicker hoarseness. This means your body might react differently to the same level of vocal use.
4. Does my heartburn make my throat problems worse genetically?
Section titled “4. Does my heartburn make my throat problems worse genetically?”Yes, your genetics can influence how severely acid reflux (GERD) impacts your throat. While GERD is a major environmental trigger, variations in genes that manage inflammation or protect laryngeal tissues, like NDST4, could make your vocal cords more sensitive to acid exposure. This means that for some people, genetic factors might amplify the damage from reflux, making chronic laryngitis symptoms more pronounced or harder to resolve.
5. Does my family’s background affect my risk for throat issues?
Section titled “5. Does my family’s background affect my risk for throat issues?”Yes, your ancestral background can play a role in your genetic risk. Studies show that genetic findings from one population group may not always apply universally to others, due to differences in gene frequencies or environmental exposures. This means certain genetic predispositions for chronic inflammatory conditions, including those affecting the throat, might be more common or expressed differently within specific ethnic groups.
6. Why do I seem so prone to getting chronic throat inflammation?
Section titled “6. Why do I seem so prone to getting chronic throat inflammation?”Your body’s overall inflammatory response and tissue resilience are partly influenced by your genes. You might have genetic variations that make your laryngeal tissues more susceptible to inflammation or slower to heal when exposed to common irritants like pollution, vocal strain, or infections. For example, differences in genes like NDST4, which is crucial for tissue health, could contribute to this increased vulnerability.
7. My sibling has it too, but why is my case so much worse?
Section titled “7. My sibling has it too, but why is my case so much worse?”Even with shared genetics, subtle differences in your specific genetic variations or how they interact with your unique environmental exposures can lead to different disease severities. You might have additional genetic factors, or even epigenetic modifications, that make your inflammatory response more intense or your vocal cords more vulnerable. Also, differences in lifestyle factors, even minor ones, can significantly impact how your genes manifest.
8. Can knowing my genes help me prevent future throat problems?
Section titled “8. Can knowing my genes help me prevent future throat problems?”Potentially, yes, but it’s still an evolving field. Understanding specific genetic predispositions—for example, if you have variations in genes like NDST4 that affect tissue maintenance or inflammation—could help you identify your personal risk factors. This knowledge might guide more targeted lifestyle adjustments or preventative strategies to reduce your exposure to specific triggers your body is genetically more sensitive to.
9. Does my body just react more strongly to irritants than others?
Section titled “9. Does my body just react more strongly to irritants than others?”Yes, your genetic makeup can definitely influence how your body reacts to various irritants. Some people have genetic variations that lead to a heightened inflammatory response or slower tissue repair in the larynx when exposed to things like smoke, pollution, or even vocal overuse. This means your vocal cords might be genetically programmed to be more sensitive or less resilient compared to others, even under similar conditions.
10. Can changing my diet or lifestyle really overcome my genetic risks?
Section titled “10. Can changing my diet or lifestyle really overcome my genetic risks?”Absolutely, lifestyle changes are crucial and often highly effective, even with genetic predispositions. While your genes might increase your susceptibility, chronic laryngitis is profoundly influenced by environmental factors like diet, smoking, and vocal habits. By actively managing these environmental triggers, you can significantly mitigate your genetic risks and reduce the likelihood of developing or worsening the condition.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Cho, Michael H., et al. “A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.” Hum Mol Genet, vol. 21, 2012, pp. 622-32.
[2] Berndt, Sonja I., et al. “Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.” Nature Genetics, vol. 45, no. 8, 2013, pp. 868-876.
[3] Dijkstra, A. E. “Susceptibility to chronic mucus hypersecretion, a genome wide association study.” PLoS One, 2014, PMID: 24714607.
[4] Chang, Shou-Wang, et al. “A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese.”PLoS One, vol. 9, no. 6, 2014, e94101.
[5] Pattaro, Cristian, et al. “Genome-wide association and functional follow-up reveals new loci for kidney function.” PLoS Genetics, vol. 8, no. 3, 2012, e1002584.
[6] Siedlinski, M., et al. “Genome-wide association study of smoking behaviours in patients with COPD.” Thorax, 2012, PMID: 21685187.
[7] Hansel, N. N., et al. “Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease.”Am J Respir Cell Mol Biol, vol. 52, no. 6, 2015, pp. 696-709.
[8] Smolonska, J., et al. “Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.”Eur Respir J, 2014, PMID: 24993907.
[9] Dijkstra, A. E., et al. “Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD.” Eur Respir J, 2015, PMID: 25234806.
[10] Gudbjartsson, D. F., et al. “Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases.”PLoS Genet, 2010, PMID: 20686651.
[11] Lee, Jin Hwa, et al. “Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.”Respir Res, vol. 15, no. 1, 2014, p. 113.
[12] Lee, J. H., et al. “IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.”Am J Respir Cell Mol Biol, vol. 52, no. 3, 2015, pp. 317-26.
[13] Cho, M. H., et al. “Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.”Lancet Respir Med, 2014, PMID: 24621683.