Kathy Low | Monash University (original) (raw)

Papers by Kathy Low

American Journal of Respiratory and Critical Care Medicine, 2019

Naessens JM, Morgenthaler TI.Analyses of the complexity of patients undergoing attended polysomno... more Naessens JM, Morgenthaler TI.Analyses of the complexity of patients undergoing attended polysomnography in the era of home sleep apnea tests.

Respirology, 2019

Background and objective: Multidisciplinary team (MDT) clinics use an integrated approach to indi... more Background and objective: Multidisciplinary team (MDT) clinics use an integrated approach to individualize care of complex medical conditions. Vocal cord dysfunction (VCD) is a challenging condition that is likely to benefit from MDT clinics but this has not been researched. Methods: A prospective observational cohort study of a novel VCD MDT clinic was conducted in patients with suspected VCD. Relevant questionnaires, medical history, physical examination, spirometry, dynamic computerized tomography (CT) larynx and laryngoscopy were utilized and patients were allocated to treatment pathways depending on putative diagnosis. Speech pathology intervention with laryngeal retraining (LR) was offered and if LR therapy failed botulinum toxin injection was offered. Primary outcome was reductions in healthcare utilization. Results: Overall, 80 consecutive patients were included in analyses. A definitive diagnosis of VCD was made in 56 of 80 (70%) patients. After LR (n = 35), emergency department (ED)/hospital admissions declined significantly in the subsequent 12 months (P = 0.001). General practice visits also reduced (P < 0.001). Botulinum toxin injections were administered in 21 patients unresponsive to LR therapy and both general practice and ED/hospital visits declined (P < 0.001 and P = 0.01, respectively) after injection. Conclusion: A multidisciplinary approach to VCD confers benefit and can be used to allocate appropriate management leading to a reduction in healthcare utilization.

Clinical & Experimental Allergy, 2015

Molecular Diagnosis & Therapy, 2017

Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhale... more Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhaled corticosteroids and long-acting beta-agonists; however, a proportion of patients are unresponsive and attain limited disease control. This group represents a considerable healthcare and financial burden, particularly patients who experience frequent exacerbations and require hospital admission. Development of new biological agents and disease biomarkers has provided novel avenues for treatment. These treatments have been highly successful, reducing exacerbations and yielding modest improvements in quality of life and lung function. However, only a proportion of severe asthmatics respond to this targeted treatment, highlighting the heterogeneity of severe asthma. One of the first biological therapies targeted immunoglobulin E (IgE) and demonstrated modest benefit but could only be used in a subgroup of patients. Recent research has shown that treatment aimed at the T helper-2-(Th 2)-high pathways and cytokines such as interleukin (IL)-5, IL-4, and IL-13 may also be effective in another partially overlapping subgroup. A blood eosinophil count over a defined threshold (generally C300 cells/ll) was a reliable biomarker and identified the majority of responders in this group. Further discovery and validation of biological markers to define asthmatic phenotypes that may benefit from biological treatments remain an area of intense interest and research. We review the latest information pertaining to biological agents and demonstrate how patient responders may potentially be identified for treatment. Key Points Severe asthmatics uncontrolled with standard treatment with long-acting beta-agonist and inhaled corticosteroids may be eligible for and responsive to biological therapies that target cytokines. Phenotyping severe asthmatics using a combination of biomarkers may be the best way to identify which patients are likely to derive benefits from targeted anti-cytokine therapy. A blood eosinophil level of C300 cells/ll is currently the most easily accessible biomarker to identify severe asthmatics who are likely to respond to biological therapies that target cytokines.

1.1 Clinical Problems, 2016

Vocal Cord Dysfunction in mild and severe asthma Introduction: Vocal cord dysfunction (VCD) cause... more Vocal Cord Dysfunction in mild and severe asthma Introduction: Vocal cord dysfunction (VCD) causes vocal cord narrowing during inspiration resulting in airflow obstruction and may contribute to breathlessness in asthma. VCD is detected in more than 40% of severe disease but it is not known if the condition is limited to severe asthma and if dysfunctional breathing is associated. Method: Patients with mild to severe asthma (total n=155) were recruited from general practice and hospital asthma clinics and spirometry was conducted. VCD was diagnosed during inspiration using dynamic 320-slice computerised tomography (CT) of the larynx, a quantitative method capable of measuring real-time vocal cord dimensions during breathing. Excessive narrowing is recognised if a predetermined lower limit of normal is exceeded. Asthma control was evaluated using ACT and ACQ5 questionnaires and dysfunctional breathing was assessed via Nijmegen questionniare. VCD was compared in asthma severity. Results: In the overall group (n=155) VCD was detected during inspiration in 42 cases (27.1%). Patients with severe uncontrolled asthma (n=68) characterised by airflow limitation (FEV 1 Conclusion: VCD is frequently detected in asthma, more so in severe disease. Airflow limitation coupled with dysfunctional breathing has a strong association with VCD. Further studies are needed to determine if VCD worsens asthma symptoms and to ascertain which treatments can improve asthma severity.

Respiratory Physiology & Neurobiology, 2018

Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional... more Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional breathing in obstructive lung diseases. However, no studies examining dysfunctional breathing in Chronic Obstructive Pulmonary Disease (COPD) have been reported. Patients with verified COPD (n = 34), asthma (n = 37) and a healthy control group (n = 41) were recruited. All participants completed the Nijmegen questionnaire for dysfunctional breathing as well as measures of disease activity. Comparisons between groups employed analysis of variance with post-hoc Bonferroni analyses and Pearson correlation for associations. Patients with COPD had significantly higher Nijmegen questionnaire scores than asthmatics (COPD: 23.4 ± 10.6 versus 17.3 ± 10.6, p = 0.016) and healthy individuals (14.3 ± 9.6, p = 0.002). Significantly more patients with COPD had severe dysfunctional breathing with Nijmegen scores > 23 (47%; 16/34) compared to asthma (27%; 10/37) and healthy controls (17%; 7/41) respectively (p = 0.019). Dysfunctional breathing was detected in ∼50% of patients with COPD, more so than in asthma or health. Strategies to reduce abnormal breathing behaviours may have important benefits for treatment of breathlessness in COPD.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Jan 24, 2016

Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called ... more Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction - VCD) leading to asthma-like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics but it is not known if PVCM is detectable in all patients with asthma-like symptoms and if the condition is more often associated with abnormal lung function. We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms or if PVCM is related to airflow limitation and/or other disease characteristics. Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n=155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionaires administer...

European Respiratory Journal, Sep 1, 2011

Traditionally the “gold standard” for detecting abnormal vocal cord movement has been laryngoscop... more Traditionally the “gold standard” for detecting abnormal vocal cord movement has been laryngoscopy. Novel dynamic 320-slice CT larynx has made it possible to quantify vocal cord movement non-invasively during inspiration and expiration. While spirometry has been useful in observing upper airway obstruction, little is known of its utility in identifying patients with abnormal vocal cord movement. Aims: To identify changes in the flow volume curve in patients with abnormal vocal cord movement (AVCM). Methods: Two groups comprising controls and asthmatics were recruited. Vocal cord abnormality was evaluated using 320-slice CT larynx. All patients had spirometry immediately prior to CT and relevant parameters were compared. Results: AVCM was not found in healthy control subjects. However, it was present in 11/23 asthmatics (50%). Discussion: While there was a significant difference in FEV1 between control and the two asthma groups, it identified obstruction alone. The only other discerning spirometric parameter was FIF50%/FEF50% which was significantly different between the control group and those with AVCM. Conclusion: Spirometric parameters appear to be poor discriminators for detecting AVCM. It may be that more sensitive lung function measures, such a resistance measured with body plethysmograph or oscillometer will be required to further discriminate between obstruction of the upper and/or lower airways.

European Respiratory Journal, Sep 1, 2012

Body: Aim: To identify asthma phenotypes in patients with refractory and non-refractory asthma in... more Body: Aim: To identify asthma phenotypes in patients with refractory and non-refractory asthma in whom inappropriate vocal cord closure and laryngeal dysfunction (LD) may occur (Low et al, AJRCCM, 2011). Methods: We evaluated 57 patients with mild to moderate non-refractory asthma (N=31) or refractory asthma (N=26). Dynamic 320 slice computerised tomography (CT) of larynx was done and a validated algorithm was used to accurately measure vocal cord lateral diameter during inspiration and expiration. Excessive narrowing of the airways was diagnosed if a predetermined lower limit of normal was exceeded. The asthma groups were compared by semi-supervised cluster analysis to identify asthma phenotypes associated with laryngeal dysfunction. Results: Overall vocal cord diameter was reduced below the lower limit of normal in 26 of 57 cases (46%). There was no relationship with asthma severity (LD) in refractory asthma: 12/26 (46%) versus non-refractory 14/31 (45%). Laryngeal dysfunction was associated with increased age (P < 0.034) bronchodilator (BD) responses <12% (P < 0.009) and difficult speech when breathless (P<0.019). There were 3 unique phenotype clusters associated with abnormal vocal cord narrowing and determinants of cluster membership were: 1. age > 40 years, female, bronchodilator response < 12%, difficulty speaking when breathless; 2. age > 40 years, bronchodilator response < 12%, BMI > 30kgs / m 2 ; 3. female, bronchodilator response < 12%, BMI > 30kgs / m 2. Conclusion: Our results indicate that vocal cord behaviour is abnormal in asthma, irrespective of severity. However, laryngeal dysfunction may often be associated with particular patient phenotypes and contribute to their overall symptomatic burden of disease.

European Respiratory Journal, Sep 1, 2012

Respirology Case Reports, 2013

Idiopathic bilateral vocal cord paralysis (VCP) is a rare and difficult condition often undiagnos... more Idiopathic bilateral vocal cord paralysis (VCP) is a rare and difficult condition often undiagnosed and frequently confused with asthma and other respiratory conditions. Accurate diagnosis is crucial since 80% of cases patients require surgical intervention, such as tracheostomy or laser surgery, to relieve symptoms. The "gold standard" for diagnosing VCP has been laryngoscopy. In this case study, we demonstrate for the first time that idiopathic bilateral VCP can be accurately diagnosed by means of a novel noninvasive methodology: dynamic volume 320slice computed tomography larynx. Three-dimensional reconstruction of laryngeal motion during the breathing cycle permitted functional assessment of the larynx showing absence of vocal cord movements. The new methodology may be valuable for noninvasive diagnosis of vocal cord movement disorders before and for follow-up after surgery.

The Lancet Respiratory Medicine, 2017

American Journal of Respiratory and Critical Care Medicine, 2019

Naessens JM, Morgenthaler TI.Analyses of the complexity of patients undergoing attended polysomno... more Naessens JM, Morgenthaler TI.Analyses of the complexity of patients undergoing attended polysomnography in the era of home sleep apnea tests.

Respirology, 2019

Background and objective: Multidisciplinary team (MDT) clinics use an integrated approach to indi... more Background and objective: Multidisciplinary team (MDT) clinics use an integrated approach to individualize care of complex medical conditions. Vocal cord dysfunction (VCD) is a challenging condition that is likely to benefit from MDT clinics but this has not been researched. Methods: A prospective observational cohort study of a novel VCD MDT clinic was conducted in patients with suspected VCD. Relevant questionnaires, medical history, physical examination, spirometry, dynamic computerized tomography (CT) larynx and laryngoscopy were utilized and patients were allocated to treatment pathways depending on putative diagnosis. Speech pathology intervention with laryngeal retraining (LR) was offered and if LR therapy failed botulinum toxin injection was offered. Primary outcome was reductions in healthcare utilization. Results: Overall, 80 consecutive patients were included in analyses. A definitive diagnosis of VCD was made in 56 of 80 (70%) patients. After LR (n = 35), emergency department (ED)/hospital admissions declined significantly in the subsequent 12 months (P = 0.001). General practice visits also reduced (P < 0.001). Botulinum toxin injections were administered in 21 patients unresponsive to LR therapy and both general practice and ED/hospital visits declined (P < 0.001 and P = 0.01, respectively) after injection. Conclusion: A multidisciplinary approach to VCD confers benefit and can be used to allocate appropriate management leading to a reduction in healthcare utilization.

Clinical & Experimental Allergy, 2015

Molecular Diagnosis & Therapy, 2017

Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhale... more Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhaled corticosteroids and long-acting beta-agonists; however, a proportion of patients are unresponsive and attain limited disease control. This group represents a considerable healthcare and financial burden, particularly patients who experience frequent exacerbations and require hospital admission. Development of new biological agents and disease biomarkers has provided novel avenues for treatment. These treatments have been highly successful, reducing exacerbations and yielding modest improvements in quality of life and lung function. However, only a proportion of severe asthmatics respond to this targeted treatment, highlighting the heterogeneity of severe asthma. One of the first biological therapies targeted immunoglobulin E (IgE) and demonstrated modest benefit but could only be used in a subgroup of patients. Recent research has shown that treatment aimed at the T helper-2-(Th 2)-high pathways and cytokines such as interleukin (IL)-5, IL-4, and IL-13 may also be effective in another partially overlapping subgroup. A blood eosinophil count over a defined threshold (generally C300 cells/ll) was a reliable biomarker and identified the majority of responders in this group. Further discovery and validation of biological markers to define asthmatic phenotypes that may benefit from biological treatments remain an area of intense interest and research. We review the latest information pertaining to biological agents and demonstrate how patient responders may potentially be identified for treatment. Key Points Severe asthmatics uncontrolled with standard treatment with long-acting beta-agonist and inhaled corticosteroids may be eligible for and responsive to biological therapies that target cytokines. Phenotyping severe asthmatics using a combination of biomarkers may be the best way to identify which patients are likely to derive benefits from targeted anti-cytokine therapy. A blood eosinophil level of C300 cells/ll is currently the most easily accessible biomarker to identify severe asthmatics who are likely to respond to biological therapies that target cytokines.

1.1 Clinical Problems, 2016

Vocal Cord Dysfunction in mild and severe asthma Introduction: Vocal cord dysfunction (VCD) cause... more Vocal Cord Dysfunction in mild and severe asthma Introduction: Vocal cord dysfunction (VCD) causes vocal cord narrowing during inspiration resulting in airflow obstruction and may contribute to breathlessness in asthma. VCD is detected in more than 40% of severe disease but it is not known if the condition is limited to severe asthma and if dysfunctional breathing is associated. Method: Patients with mild to severe asthma (total n=155) were recruited from general practice and hospital asthma clinics and spirometry was conducted. VCD was diagnosed during inspiration using dynamic 320-slice computerised tomography (CT) of the larynx, a quantitative method capable of measuring real-time vocal cord dimensions during breathing. Excessive narrowing is recognised if a predetermined lower limit of normal is exceeded. Asthma control was evaluated using ACT and ACQ5 questionnaires and dysfunctional breathing was assessed via Nijmegen questionniare. VCD was compared in asthma severity. Results: In the overall group (n=155) VCD was detected during inspiration in 42 cases (27.1%). Patients with severe uncontrolled asthma (n=68) characterised by airflow limitation (FEV 1 Conclusion: VCD is frequently detected in asthma, more so in severe disease. Airflow limitation coupled with dysfunctional breathing has a strong association with VCD. Further studies are needed to determine if VCD worsens asthma symptoms and to ascertain which treatments can improve asthma severity.

Respiratory Physiology & Neurobiology, 2018

Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional... more Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional breathing in obstructive lung diseases. However, no studies examining dysfunctional breathing in Chronic Obstructive Pulmonary Disease (COPD) have been reported. Patients with verified COPD (n = 34), asthma (n = 37) and a healthy control group (n = 41) were recruited. All participants completed the Nijmegen questionnaire for dysfunctional breathing as well as measures of disease activity. Comparisons between groups employed analysis of variance with post-hoc Bonferroni analyses and Pearson correlation for associations. Patients with COPD had significantly higher Nijmegen questionnaire scores than asthmatics (COPD: 23.4 ± 10.6 versus 17.3 ± 10.6, p = 0.016) and healthy individuals (14.3 ± 9.6, p = 0.002). Significantly more patients with COPD had severe dysfunctional breathing with Nijmegen scores > 23 (47%; 16/34) compared to asthma (27%; 10/37) and healthy controls (17%; 7/41) respectively (p = 0.019). Dysfunctional breathing was detected in ∼50% of patients with COPD, more so than in asthma or health. Strategies to reduce abnormal breathing behaviours may have important benefits for treatment of breathlessness in COPD.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Jan 24, 2016

Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called ... more Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction - VCD) leading to asthma-like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics but it is not known if PVCM is detectable in all patients with asthma-like symptoms and if the condition is more often associated with abnormal lung function. We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms or if PVCM is related to airflow limitation and/or other disease characteristics. Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n=155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionaires administer...

European Respiratory Journal, Sep 1, 2011

Traditionally the “gold standard” for detecting abnormal vocal cord movement has been laryngoscop... more Traditionally the “gold standard” for detecting abnormal vocal cord movement has been laryngoscopy. Novel dynamic 320-slice CT larynx has made it possible to quantify vocal cord movement non-invasively during inspiration and expiration. While spirometry has been useful in observing upper airway obstruction, little is known of its utility in identifying patients with abnormal vocal cord movement. Aims: To identify changes in the flow volume curve in patients with abnormal vocal cord movement (AVCM). Methods: Two groups comprising controls and asthmatics were recruited. Vocal cord abnormality was evaluated using 320-slice CT larynx. All patients had spirometry immediately prior to CT and relevant parameters were compared. Results: AVCM was not found in healthy control subjects. However, it was present in 11/23 asthmatics (50%). Discussion: While there was a significant difference in FEV1 between control and the two asthma groups, it identified obstruction alone. The only other discerning spirometric parameter was FIF50%/FEF50% which was significantly different between the control group and those with AVCM. Conclusion: Spirometric parameters appear to be poor discriminators for detecting AVCM. It may be that more sensitive lung function measures, such a resistance measured with body plethysmograph or oscillometer will be required to further discriminate between obstruction of the upper and/or lower airways.

European Respiratory Journal, Sep 1, 2012

Body: Aim: To identify asthma phenotypes in patients with refractory and non-refractory asthma in... more Body: Aim: To identify asthma phenotypes in patients with refractory and non-refractory asthma in whom inappropriate vocal cord closure and laryngeal dysfunction (LD) may occur (Low et al, AJRCCM, 2011). Methods: We evaluated 57 patients with mild to moderate non-refractory asthma (N=31) or refractory asthma (N=26). Dynamic 320 slice computerised tomography (CT) of larynx was done and a validated algorithm was used to accurately measure vocal cord lateral diameter during inspiration and expiration. Excessive narrowing of the airways was diagnosed if a predetermined lower limit of normal was exceeded. The asthma groups were compared by semi-supervised cluster analysis to identify asthma phenotypes associated with laryngeal dysfunction. Results: Overall vocal cord diameter was reduced below the lower limit of normal in 26 of 57 cases (46%). There was no relationship with asthma severity (LD) in refractory asthma: 12/26 (46%) versus non-refractory 14/31 (45%). Laryngeal dysfunction was associated with increased age (P < 0.034) bronchodilator (BD) responses <12% (P < 0.009) and difficult speech when breathless (P<0.019). There were 3 unique phenotype clusters associated with abnormal vocal cord narrowing and determinants of cluster membership were: 1. age > 40 years, female, bronchodilator response < 12%, difficulty speaking when breathless; 2. age > 40 years, bronchodilator response < 12%, BMI > 30kgs / m 2 ; 3. female, bronchodilator response < 12%, BMI > 30kgs / m 2. Conclusion: Our results indicate that vocal cord behaviour is abnormal in asthma, irrespective of severity. However, laryngeal dysfunction may often be associated with particular patient phenotypes and contribute to their overall symptomatic burden of disease.

European Respiratory Journal, Sep 1, 2012

Respirology Case Reports, 2013

Idiopathic bilateral vocal cord paralysis (VCP) is a rare and difficult condition often undiagnos... more Idiopathic bilateral vocal cord paralysis (VCP) is a rare and difficult condition often undiagnosed and frequently confused with asthma and other respiratory conditions. Accurate diagnosis is crucial since 80% of cases patients require surgical intervention, such as tracheostomy or laser surgery, to relieve symptoms. The "gold standard" for diagnosing VCP has been laryngoscopy. In this case study, we demonstrate for the first time that idiopathic bilateral VCP can be accurately diagnosed by means of a novel noninvasive methodology: dynamic volume 320slice computed tomography larynx. Three-dimensional reconstruction of laryngeal motion during the breathing cycle permitted functional assessment of the larynx showing absence of vocal cord movements. The new methodology may be valuable for noninvasive diagnosis of vocal cord movement disorders before and for follow-up after surgery.

The Lancet Respiratory Medicine, 2017