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\begin{document}

\title{Allergy and Chronic Throat Symptoms: a Primer For Clinicians}



\author[1]{Nathan Quigley}%
\author[2]{Sandeep Mistry}%
\author[1]{Sarju Vasani}%
\affil[1]{The University of Queensland Faculty of Medicine}%
\affil[2]{Bradford Teaching Hospitals}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Chronic throat symptoms such as cough, dysphonia, globus sensation,
throat clearing and sensation of mucus in the throat are prevalent and
bothersome symptoms, which are now understood to cause significant
morbidity when untreated. A dilemma for clinicians is the frequent lack
of organic or structural disease explanation for these non-specific
symptoms, even with often multidisciplinary assessment. Whilst
associations to reflux or functional syndromes are often implied, these
diagnostic paradigms lack interdisciplinary consensus and rely on
empirical practices in the absence of clear disease links. The role of
respiratory allergy or respiratory allergy sensitisation in contributing
to presentations involving unexplained chronic throat symptoms (UCTS)
remains poorly defined, but is emerging as a potentially undervalued
relationship. For the clinician, clinical considerations and potential
therapeutic strategies for the patient with UCTS and respiratory allergy
disease or sensitisation remain ambiguous concepts, devoid of consensus
or guidelines. This scoping review addresses the intersection of
respiratory allergy and chronic throat complaints, offering an
up-to-date assessment of this potential relationship, postulated symptom
mechanisms and evidence to guide therapeutic decisions.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Chronic symptoms affecting the aerodigestive tract, such as persistent
cough, dysphonia, globus sensation, dysphagia, and throat clearing, are
frequently encountered in non-acute clinical settings. Their
non-specific nature poses diagnostic challenges, often requiring
multidisciplinary evaluations that may yield inconclusive
results{[}\emph{1-3} {]}. Aetiological uncertainty in these scenarios of
Unexplained Chronic Throat Symptoms (UCTS) emerge as a challenging
clinical entity, given increasing recognition of their prevalence and
substantial morbidity{[}\emph{2} , \emph{4-8} {]}. Some authors estimate
patients with UCTS account for as many as 5-10\% of total primary care
presentations{[}\emph{2} {]}, indicating this localised symptom
constellation is of significant public health importance. Diagnostic
uncertainties often lead to provisional diagnoses predicated on
empirical associations with gastroesophageal reflux (GORD) or various
functional aerodigestive disorders, often without unified
interdisciplinary guidance{[}\emph{2} , \emph{9-13} {]}.

Amongst various competing aetiological hypotheses for UCTS, the role of
respiratory allergies remains under-represented in current scientific
discourse{[}\emph{14-20} {]}. Preliminary evidence indicates a higher
prevalence of sensitisation to airborne allergens among UCTS patients
compared to non-allergic cohorts {[}\emph{14} , \emph{16} , \emph{18}
,\emph{20-23} {]}. In the absence of a distinct laryngopharyngeal
allergy phenotype, it is often postulated that these irritative symptoms
may relate to secondary impacts of

type 2 inflammation in the nasal and/or lower airways{[}\emph{24-26}
{]}. However, existing clinical guidelines seldom address this
association directly, with the exception of the somewhat controversial
''Upper Airway Cough Syndrome (UACS),'' which correlates persistent
cough with inflammatory nasal conditions, such as allergic rhinitis (AR)
or rhinosinusitis (ARS){[}\emph{14} , \emph{24-26} {]}.

Over the past two decades, the notion of Allergic Laryngitis (AL) as a
distinct laryngopharyngeal allergic disease phenotype has gained
scholarly attention. Emerging data substantiate AL as a plausible and
potentially under diagnosed entity in UCTS patients with concomitant
airway allergies{[}\emph{14-21} , \emph{23} {]}. Nevertheless, the
clinical implications of the elevated incidence of UCTS among patients
with respiratory allergies remain unclear, particularly regarding
therapeutic strategies.

This review aims to coherently synthesize extant evidence on the complex
interrelationship between respiratory allergies and UCTS when other
aetiologies are absent. Additionally, we critically appraise the
literature for the impact of current allergy therapies on chronic throat
symptoms in respiratory allergy patients. The overarching goal is to
equip healthcare practitioners with a rational basis for considering
allergies as a potential aetiological contributor in UCTS, while
offering evidence-based therapeutic guidance for such cases.

\textbf{Method}

We undertook a comprehensive scoping review of the literature addressing
respiratory allergies and chronic throat complaints. Recognizing the
challenges posed by inconsistent terminology and the topic's
underrepresentation, our approach was iterative and adaptive.

We utilized an array of keyword and search string combinations,
including specific terms for respiratory allergies such as 'airway
allergy', 'asthma', 'allergic rhinitis', and 'allergic laryngitis'. For
chronic throat symptoms, we incorporated key terms such as 'dysphonia',
'globus sensation', 'dysphagia', and 'irritable larynx'.

When exploring therapeutic strategies, we expanded our search to include
key treatment terms, for example 'inhalers', 'antihistamines',
`immunotherapy' and 'leukotriene antagonists'.

Our iterative search process was supplemented by manual citation
analysis from shortlisted studies. This continued until no additional
pertinent studies emerged. The primary author initially screened studies
by title and abstract. Final study inclusion was determined through a
consensus review, ensuring relevance to our research focus.

\textbf{Investigating the relationship between Respiratory Allergy and
Unexplained Chronic Throat Symptoms (UCTS)}

\textbf{Type 2 Inflammation of the Nasal Airway: impacts on the
Laryngopharynx}

Allergic rhinitis (AR) impacts approximately 40\% of the general
population {[}\emph{27} , \emph{28} {]}. In sensitised patients,
exposure to airborne allergens triggers an IgE-mediated immune response,
leading to mast cell de-granulation and release of inflammatory
mediators like histamine. This culminates in nasal mucosal inflammation,
resulting in clinical symptoms such as rhinorrhoea, sneezing, and nasal
congestion. In patients with allergic rhinosinusitis (ARS), this
reaction extends to the paranasal sinuses, and may result in additional
symptoms of headache, facial pain and or fullness.

\textbf{Table 1} summarises research data reporting the prevalence of
chronic throat symptoms in this population. Beyond the nose, chronic
cough is recognised as a potential sequelae of inflammatory nasal
disease, including allergic nasal phenotypes. Refractory cough in this
setting is often enveloped under the Upper Airway Cough Syndrome (UACS)
umbrella, which links refractory cough without structural or other
disease explanations with chronic nasal inflammation, of which allergy
is a key aetiology{[}\emph{24-26} , \emph{29} {]}. We found non-cough
aerodigestive symptoms are infrequently sought and minimally reported in
the setting of allergic nasal disease, despite observations that
refractory cough is often accompanied by additional localised throat
symptoms{[}\emph{30} , \emph{31} {]}. Considering this limitation, it
nonetheless would appear that non-specific complaints involving
unexplained dysphonia, globus, mucus sensation, throat clearing and
other irritative UCTS are equally prevalent in this cohort.

\textbf{Type 2 Inflammation of the Lower Airways: impacts on the
Laryngopharynx}

Asthma affect up to one fifth of the general population{[}\emph{32} {]},
characterized by airway hyper responsiveness and reversible pulmonary
function impairments on spirometry{[}\emph{33} {]}. Classical lower
airway symptoms including cough, wheezing, and dyspnoea. Non-asthma
variants also characterised by lower airway eosinophilia have been
identified, including cough-variant asthma (CVA) and non-asthma
eosinophilic bronchitis (NAEB), also termed atopic cough (AC). In CVA,
patients present with cough but no airway limiting symptoms, and
reversible pulmonary function impairments{[}\emph{33} {]}. In NAEB/AC,
chronic cough with sputum and bronchial eosinophilia {[}\emph{34} {]}
occurs without the pulmonary function impairments seen in asthma and
CVA. In these disorders, cough is a primary symptom related to lower
airway type 2 inflammation, and thus is excluded from our analysis
in\textbf{Table 1} . The prevalence of non-cough UCTS in lower airway
were infrequently reported, and available data predominantly concerns
studies of asthma patients, with most attention given to voice related
complaints. In general, data presented in \textbf{Table 1} re-iterates a
view that non-cough symptoms are more prevalent in populations with
lower airway allergy.

\textbf{Allergen-Mucosal interactions within the Laryngopharynx: the
case for a distinct Allergy Phenotype}

While the laryngopharyngeal mucosa shares anatomical continuity with the
nasal and lower airway epithelium, few studies have investigated its
potential for an inherent IgE-mediated response to inhaled allergens in
sensitised individuals{[}\emph{14} , \emph{16} , \emph{23} {]}. Recent
reviews provide comprehensive insights into this topic {[}\emph{14}
,\emph{16} , \emph{18-21} , \emph{23} , \emph{35} , \emph{36} {]}.
Collectively, these studies highlight epidemiological data which implies
elevated respiratory allergy prevalence within UCTS populations and
underscore the presence of mast cells within the laryngopharyngeal
mucosa. Further reference is made to small scale provocation data which
identifies eosinophilic inflammation of laryngopharyngeal tissues
following allergen exposure in both animal and preliminary human
studies. Collectively, this small but emerging literature offers a
unified position which posits the existence of a distinct and
potentially overlooked phenotype of respiratory allergy, provisionally
termed 'Allergic Laryngitis' (AL).

\textbf{Chronic Throat Symptoms: Mechanisms in Allergy}

The data summarised in \textbf{Table 1} suggests that patients with
airway allergy experience increased rates of chronic, irritative throat
symptoms in the absence of other discernible organic causes. Cough is
the symptom most widely reported, which is unsurprising given its
significance in lower airway disease. Nonetheless, various and often
concurrent throat complaints such as globus, dysphonia, mucus sensation,
throat clearing and others equally troublesome for this patient group.
Potential mechanisms postulated to underpin the relationship between
allergy and UCTS, as show in \textbf{Figure 1} , are summarised below.

\textbf{Primary Symptoms}

IgE mediated Type 2 inflammation of the Laryngopharynx Though AL is not
yet widely accepted as a form or phenotype of airway allergy, the
capacity for the laryngopharynx to mount a type 2 IgE mediated
inflammatory reaction in the presence of inhaled allergens appears
plausible, bolstered by observed eosinophilic inflammatory reactions in
several small human and animal provocation studies{[}\emph{14},
\emph{16}, \emph{23}{]}. The laryngopharynx, in keeping with its
continuity with nasal and bronchial airways, is populated with mast
cells and goblet cells{[}\emph{19}, \emph{20},\emph{23}{]}, and the
laryngeal inlet by virtue of its function is routinely exposed to
deposition of inhaled particulates and antigens, exacerbated in patients
with nasal allergy and resulting nasal obstruction. Further
investigation is required to determine the significance of potential
primary mucosal-allergen interactions in this setting, given
implications both for therapy and for united airway interactions.

\textbf{Secondary Symptoms}

Mucus Trafficking through the Laryngopharynx IgE-mediated histamine
liberation, in conjunction with other inflammatory mediators,
precipitates mucosal oedema, augmented mucus secretion, bronchial smooth
muscle constriction, and airway architectural alterations in both the
nasal and bronchopulmonary regions{[}\emph{34}, \emph{37-40}{]}.
Enhanced mucus translocation from the bronchi or nasal cavity towards
the larynx may instigate epithelial irritation, compromise glottic
closure, and provoke airway reflexive responses, culminating in a
diverse array of aerodigestive manifestations{[}\emph{25}, \emph{41}{]}.
Although post-nasal drip (PND) is posited as a pivotal component of the
UACS hypothesis, its attribution as the aetiological agent for symptoms
such as throat clearing and cough in patients with AR and ARS remains a
subject of academic debate, especially when nasoendoscopic observations
do not corroborate anomalous secretions{[}\emph{26}{]}. Additionally,
the UACS paradigm may be insufficient in addressing the multifaceted
symptomatology accompanying or occurring independently of cough in UTCS.
Nasal Airflow Obstruction Nasal congestion in AR leads to a compensatory
shift towards oral respiration, bypassing the nasal humidification and
filtration mechanisms. This change may undermine the laryngopharyngeal
epithelial barrier by promoting mucosal desiccation, increasing allergen
deposition in the aerodigestive tract, and exacerbating lower airway
constriction {[}\emph{28}{]}. Secondary Phonotrauma Phonotrauma, often
linked to vocal misuse or overuse{[}\emph{42}{]}., refers to epithelial
damage induced by excessive vocal cord vibrations or
contact{[}\emph{43}{]} {[}\emph{44}{]}. Chronic airway symptoms such as
persistent cough and throat clearing, which necessitate robust laryngeal
contraction and elevated glottic pressure, can secondarily induce
phonotrauma{[}\emph{44}{]}. This may initiate a self-sustaining feedback
loop of irritation and reflexive symptoms over time, as depicted in
\textbf{Figure 2} {[}\emph{45}{]} {[}\emph{46}{]}. United Airway effects
A growing corpus of literature advocates for the ''Unified Airway
Model,'' in which different segments of the respiratory tract are
considered as functionally interconnected{[}\emph{40}, \emph{47},
\emph{48}{]}. Inflammatory mediators, specifically vascular cytokines,
circulate locally, enabling inflammation in one segment to influence
others. While this concept has been well-studied in the context of lower
airway and nasal interactions{[}\emph{29}, \emph{39}, \emph{48}{]}, its
implications for the laryngopharynx remain largely unexplored yet offer
a plausible mechanism linking nasal and lower airway inflammation with
non-specific chronic laryngitis.

\textbf{The role of Airway Hypersensitivity: relevance in Allergy}

The theory of airway hypersensitisation posits a heightened sensitivity
in laryngeal and pharyngeal tissues as a potential aetiological factor
for UCTS{[}\emph{4} , \emph{6} , \emph{11} , \emph{49-54} {]}.
Underlying this theory is the concept that peripheral and/or central
sensitization of neuronal pathways results in exaggerated afferent nerve
activity, transforming normally non-noxious stimuli into distressing
symptoms{[}\emph{11} , \emph{28} , \emph{55} , \emph{56} {]}. This state
may arise from an initial insult including viral infection, allergy, or
acid reflux, but persists even after the resolution of the original
trigger, and is likely modulated by complex biopsychosocial factors.
Consequently, the sensitized airway tissues may be reactive to various
dietary, endogenous and environmental irritants and in some cases by
innocuous stimuli (such as phonation or emotion), leading to persistent,
often refractory symptoms that defy conventional diagnostic
categorization and therapeutic approaches. The role of allergy in
precipitating or contributing to somatosensory aberrations, or indeed
the role of sensitisation in the occurrence or expression of throat
symptoms in this group is poorly understood at present.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1. Aerodigestive symptom mechanisms in lower airway and nasal
allergic disease

Figure 2. Phonotraumatic symptoms as a source of self-sustaining chronic
laryngeal irritation\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Table 1. Reported association between eosinophilic airway
disease variants and chronic aerodigestive symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Table 1. Reported association between eosinophilic airway
disease variants and chronic aerodigestive symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Table 1. Reported association between eosinophilic airway
disease variants and chronic aerodigestive symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Table 1. Reported association between eosinophilic airway
disease variants and chronic aerodigestive symptoms}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Chronic cough}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Vocal symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Sensory symptoms (globus, tickle, catarrh sensation, urge to
clear throat)}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Nasal allergy}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Numerous studies identify chronic cough as a primary symptom of
AR/ACRS{[}\emph{57}{]} {[}\emph{24}{]} {[}\textbf{58}{]} {[}\emph{38}{]}
{[}\emph{59}{]} {[}\emph{60}{]} {[}\emph{29}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
AR patients show subjective and objective derangements of voice quality.
VHI scores show increase, while VS parameters do not change with the
severity of AR.{[}\emph{61}{]} Mean VHI score (p=0.001) were
significantly higher in the \emph{allergic rhinitis} group than in
controls.{[}\emph{62}{]} Patients with either AR or NAR had higher odds
of dysphonia (odds ratio, 4.22; 95\% confidence interval, 1.03 to 17.32)
when confounding variables such as asthma, inhaled steroid use, and
gastroesophageal reflux are controlled for,.{[}\emph{47}{]} In a cohort
with non-structural dysphonia, AR was detected at three times the rate
of LPR.{[}\emph{35}{]} {[}2{]}Both subjective and objective voice
parameters were impaired in AR patients during pollen season, and in
both measures this improved to near control levels after treatment
{[}\emph{63}{]} Results showed that in singers with AR both nasal (TNS
of 4.0 \selectlanguage{ngerman}± 2.4 vs. 0.0 ± 0.0, p \textless{} 0.05) and laryngeal complaints
(TLS of 1.4 ± 1.1 vs. 0.0 ± 0.2, p \textless{} 0.05) were induced at 3
min after the provocation. The induced laryngeal complaints were the
feeling of laryngeal irritation, secretions and
globus.~{[}\emph{64}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Results showed that in singers with AR both nasal (TNS of 4.0 \selectlanguage{ngerman}± 2.4 vs.
0.0 ± 0.0, p \textless{} 0.05) and laryngeal complaints (TLS of 1.4 ±
1.1 vs. 0.0 ± 0.2, p \textless{} 0.05) were induced at 3 min after the
provocation. The induced laryngeal complaints were the feeling of
laryngeal irritation, secretions and globus.~{[}\emph{64}{]} Dysphonia,
frequent throat cleaning, and a globus sensation are common
presentations of LPR and allergic rhinitis/laryngitis. and allergic
rhinitis/laryngitis.~{[}\emph{17}{]} Subjective sensory symptoms of
itch, irritation, mucus sticking in the throat are reported in 33-82\%
of patients with allergic rhinitis{[}\emph{36}{]} In patients with birch
pollinosis AR, 55\% reported laryngeal symptoms such as cough, itch and
globus. {[}\emph{65}{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Lower airway allergy}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{\#\#}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
In asthmatic patients, maximum phonation time, frequency, and amplitude
perturbation parameters were impaired, but the vital capacity and the
duration of illness did not correlate with these
findings.{[}\emph{66}{]} {[}2{]}Values for F0, jitter, and shimmer were
very similar between asthmatics and non-asthmatics, but there were
statistically significant differences in values for harshness,
hoarseness, NNE, S/Z ratio (all p 0.01), and breathiness (p = 0.015).
Findings suggest that lower airway diseases such as asthma can impair
phonation. {[}\emph{67}{]}. Dysphonia is significantly more prevalent in
patients with asthma compared to controls.{[}\emph{68}{]}
{[}2{]}Compared with non-asthma participants, asthma patients who had
not taken asthma medication recently showed a higher AOR (1.62; 95\% CI
= 1.0--2.42) for dysphonia, and asthma patients who had taken asthma
medication recently showed the highest adjusted odds ratio for dysphonia
(AOR = 1.97; 95\% confidence interval, CI = 1.28--3.02, P =
0.001).~{[}\emph{69}{]} Vocal morbidity is common in patients with
asthma, and should not be immediately attributed to steroid-related
candidiasis.{[}\emph{5}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Laryngeal hypersensitivity and impaired voice measures were common in
severe asthma.{[}\emph{70}{]} Laryngeal sensory symptoms in patients
with classical asthma (CA) or cough predominant asthma (CPA) were
reported as follows CA: Itchy throat 44\% Abnormal sensations 30\%
recurrent throat clearing 27\% sensation of mucus in the throat 30.2\%
CPA: Itchy throat 56.5\%, abnormal sensations in the throat 30\%,
recurrent throat clearing 32.5\%, sensation of mucus in the throat
31.5\% {[}\emph{33}{]} Both laryngeal allergy and AC are associated with
persistent dry cough, globus, atopic factors, the absence of bronchial
hyperresponsiveness, and are responsive to antihistamines.
{[}\emph{71}{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{\#\# Cough related data was omitted in the case of Lower Airway
Allergy} \emph{VHI: Vocal handicap index VS: Vocal stroboscopy}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{\#\# Cough related data was omitted in the case of Lower Airway
Allergy} \emph{VHI: Vocal handicap index VS: Vocal stroboscopy}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{\#\# Cough related data was omitted in the case of Lower Airway
Allergy} \emph{VHI: Vocal handicap index VS: Vocal stroboscopy}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{\#\# Cough related data was omitted in the case of Lower Airway
Allergy} \emph{VHI: Vocal handicap index VS: Vocal stroboscopy}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Treating Respiratory Allergic Disease: Impacts on Chronic Throat
Symptoms}

\textbf{Nasal Allergy Treatments}

Current guidelines recommend intranasal corticosteroids and nasal
irrigation as first line therapies for AR and ARS. Additional
therapeutic options may involve intranasal or systemic antihistamine
treatments, leukotriene antagonists, systemic corticosteroids,
immunotherapy and biological therapies, as well as surgery. Table 2
summarises research findings from AR/ARS treatment studies which report
throat symptoms as primary or secondary treatment outcomes, as well as
relevant recommendations derived from consensus guidelines. In general,
this literature is sparse and challenging to identify, with dominant
consideration given to cough within the UACS context. Some data
indicates that patients with AR may benefit from additional adjunct
treatment strategies additional to intranasal corticosteroids in order
to maximally address additional throat complaints, including
antihistamines and leukotriene antagonists, though insufficient evidence
is identified to provide recommendations. The role of immunotherapy and
other novel allergy treatment strategies for this purpose remains
uncertain without research attention.

\textbf{Lower Airway Allergy Treatments}

Cough is the primary symptom outcome of interest in lower airway
allergy, alongside airway limitation symptoms. Inhaled corticosteroids
and bronchodilators (particularly beta-2 agonists) are the mainstay of
treatment, but a range of alternative and adjucnt treatments options
exist, inclusive of systemic corticosteroids, antihistamines, inhaled
bronchodilators, inhaled or systemtic anti-muscarinic agents and
immunotherapy. We struggled to identify meaningful data which reports
treatment impacts on persistent irritative UCTS in this setting, beyond
those studies which note deleterious effects on inhaled corticosteroids
on voice parameters. One study {[}\emph{45} {]} found patients
undergoing immunotherapy for asthma and other airway allergy phenotypes
reported reduced vocal symptoms in proportion to treatment duration,
including lower reliance on inhaled corticosteroids. This may be of
significance in patients reliant on inhaled corticosteroids in whom
chronic dysphonia is a complaint, but further research is necessary to
guide recommendation. Outside of cough, treatment considerations or
adjuncts which account for for chronic throat complaints in the patient
with bronchopulmonary allergy remain undefined.

\textbf{Allergic Laryngitis}

To the best of our assessment, there is no treatment data available
which reports symptom outcomes in patients treated for suspected primary
laryngeal allergy.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Table 2. Allergy treatments and their impact on throat
symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Table 2. Allergy treatments and their impact on throat
symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Table 2. Allergy treatments and their impact on throat
symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Table 2. Allergy treatments and their impact on throat
symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Table 2. Allergy treatments and their impact on throat
symptoms}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Study description}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Allergic population}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Allergy therapy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Outcomes reported}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Recommendation}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Systematic review of RCTs {[}\emph{72}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{AR / AC}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
nsH1RAs\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Only 3 RCTs were identified to include validated cough measures at
baseline and post treatment. All reported significant improvements in
subjective cough scores; atopic cough (relative improvement in cough
frequency score: 36.6 8.4\%) seasonal allergic rhinitis-associated cough
(cough frequency score: 44.0 7.3\% and cough intensity score: 65.7
8.3\%); allergic rhinitis patients with comorbid asthma (4.0
1.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Few clinical trials examining the benefits of nsH1RAs on chronic cough
outcomes have been conducted. There may be a subgroup of patients,
particularly those with seasonal AR related cough or atopic cough, whose
cough may improve with nsH1RA treatment. Further research is
required.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Prospective case series {[}\emph{63}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{AR}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
INCS and Loratadine\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Improvement in both subjective and objective voice parameters during
pollen season.\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
The voice quality of patients with AR is improved with medical
treatment.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Korean cough guidelines {[}\emph{73}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{UACS (AR)}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Various\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{For patients with suspected UACS} - \emph{Intranasal steroid} can
be considered in order to improve cough (evidence, very low;
recommendation, weak). - \emph{Oral anti-histamine} is recommended to
improve cough (evidence, very low; recommendation, strong). -
\emph{Nasal decongestant} monotherapy is not recommended to improve
cough (evidence, expert opinion; recommendation, strong). -
\emph{Intranasal antihistamine} is not considered to improve cough
(evidence, very low; recommendation, weak). - \emph{Antibiotics} are not
recommended to improve cough (evidence, expert opinion; recommendation,
strong).\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Prospective case series \emph{50}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
AR\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Nasal saline nasopharyngeal irrigation (NSNPI) OR fluticasone propionate
nasal spray (FPNS)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Patients with suspected AR to house-dust mite reported less cough
symptoms after both interventions. VAS and nasal lavage inflammatory
markers showed significant improvement or change in both. Overall, a
better relief of the cough symptom after 30 days of treatment with NSNPI
compared with FPNS\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
NSPI reduces chronic cough in AR, more so than FNPS treatment\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prospective cohort study {[}\emph{74}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{UACS (AR)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Montelukast 10mg daily\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Cough symptoms were significantly reduced in patients with UACS or LPR,
but not asthma. Treatment led to reductions in lactoferrin and ECP
levels, but not MPO. Pulmonary function was not affected by
treatment,\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Monteleukast treatment improves cough in patients with UACS but not
asthma\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ARIA clinical guidelines {[}\emph{75}{]}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{UACS (AR)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Various\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Patients with UACS should be prescribed a trial of nasal corticosteroids
and/or antihistamines for at least 4 weeks\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Discussion}

Chronic throat symptoms, when unexplained and devoid of structural or
malignant origins, are often dismissed as minor irritations. However,
their prevalence and substantial morbidity for affected patients are now
increasingly recognized. The absence of a standardized terminology for
these localized and often vague aerodigestive complaints may contribute
to underestimation of their public health significance. The prevailing
focus on empirical diagnoses of laryngopharyngeal reflux or functional
throat disorders has led to divergent specialty treatments may
contribute to patient dissatisfaction with inconsistent symptom relief
and varying degrees of medical skepticism.

Among the proposed aetiologies for UCTS, the role of allergies continues
to remain relatively under-explored.

Key observations from our review include. UCTS, inclusive of dysphonia,
cough, globus sensation, dysphagia, throat clearing and others appear to
be prevalent in patients with respiratory allergies compared to general
populations.

The current discourse on the allergy-UCTS association bifurcates by
primary and secondary symptom mechanisms. Primary symptoms point to
IgE-mediated mucosal reactions upon exposure to aerosolised allergens in
sensitized individuals, provisionally termed ''Allergic Laryngitis.''
Preliminary data from both animal and human studies support this
emerging theory, but additional dedicated research is needed to
elucidate this concept and determine its clinical significance,
especially regarding treatment implications.

Several theories likewise identify potential interactions between type 2
inflammation in the nasal or bronchopulmonary lining and the
laryngopharynx as a cause of non-specific throat symptoms. Their
clinical relevance to the patient with UCTS remains inadequately
defined, but nonetheless contributes to the contention that allergy may
be under-recognised as an aetiologic factor in such scenarios.

Current clinical guidelines for treatment of AR/ARS and lower airway
allergy phenotypes largely overlook UCTS, indicating a potential
interdisciplinary treatment gap. Existing treatment approaches targeting
nasal and lower airway Type 2 inflammation might not adequately address
laryngopharyngeal issues or a primary mucosal IgE-mediated process. This
literature review reveals limited evidence concerning efficacy of
current treatment options for throat symptoms in allergic patients,
precluding provision of evidence-based recommendations. Moreover, some
allergy treatments, like inhaled corticosteroids and systemic
antihistamines, might exacerbate laryngopharyngeal symptoms in UCTS
patients. At present the efficacy of therapies targeting airway
hypersensitivity in UCTS and allergy remains uncertain.

We suggest based on the findings in this review that the role of allergy
in contributing to chronic aerodigestive complaints, and the appropriate
therapeutic response in these scenarios remains a significant area of
unmet research need.

\textbf{Conclusion}

The prevailing medical literature predominantly overlooks potential
ramifications of nasal and lower airway allergies on the laryngopharynx.
There exists a plausible mechanistic interplay linking IgE mediated
inflammation of these regions to diverse UCTS manifestations, yet
contemporary guidelines rarely address this non-specific but significant
symptom group. Furthermore, the dynamics of allergen-mucosal
interactions within the laryngopharynx, which might precipitate chronic
or episodic mucosal inflammation, remain inadequately explored,
notwithstanding emerging supportive evidence. Standard therapeutic
interventions for nasal or bronchopulmonary allergy may not
comprehensively address laryngopharyngeal symptoms and could, in certain
instances, exacerbate them. For patients presenting with UCTS, the
concurrent presence of airway allergies introduces a dimension of
clinical ambiguity, underscoring the imperative for increased research
attention to guide practice and therapeutic approaches.

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